1c1c - Revision history

OCA at 15:37, 13 March 2024

OCA — Wed, 13 Mar 2024 15:37:46 GMT

←Older revision		Revision as of 15:37, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='1c1c' size='340' side='right'caption='[[1c1c]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='1c1c' size='340' side='right'caption='[[1c1c]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1c1c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~9hiv1 9hiv1~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C1C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C1C FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1c1c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C1C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C1C FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=612:6-(CYCLOHEXYLSULFANYL)-1-(ETHOXYMETHYL)~~-5~~-(1-METHYLETHYL)PYRIMIDINE-2,4(1H,3H)-DIONE'>612</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.5Å</td></tr>
-	<tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=~~CSD~~:3-~~SULFINOALANINE~~'>~~CSD~~</scene><~~/td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=612:6-(CYCLOHEXYLSULFANYL)-1-(ETHOXYMETHYL)-5-(1-METHYLETHYL)PYRIMIDINE-2,4(1H,3H)-DIONE'>612</scene>, <scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr>
-	~~<tr id~~='~~related'><td class~~=~~"sblockLbl"><b>[[Related_structure\|Related~~:~~]]</b></td><td class="sblockDat"><div style='overflow: auto; max~~-~~height: 3em;~~'>[[1rtv\|1rtv]], [[1rth\|1rth]], [[1vru\|1vru]], [[1rti\|1rti]], [[1rtj\|1rtj]], [[1rev\|1rev]], [[1rt1\|1rt1]], [[1rt2\|1rt2]], [[1klm\|1klm]], [[1rt3\|1rt3]], [[1rt4\|1rt4]], [[1rt5\|1rt5]], [[1rt6\|1rt6]], [[1rt7\|1rt7]], [[1c0t\|1c0t]], [[1c0u\|1c0u]], [[1c1b\|1c1b]]</~~div></td></tr>~~	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] </span></td></tr>	+
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1c1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c1c OCA], [https://pdbe.org/1c1c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c1c RCSB], [https://www.ebi.ac.uk/pdbsum/1c1c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c1c ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1c1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c1c OCA], [https://pdbe.org/1c1c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c1c RCSB], [https://www.ebi.ac.uk/pdbsum/1c1c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c1c ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/POL_HV1H2 POL_HV1H2]] Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to play a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. It binds in the cytoplasm the human BAF protein which prevent autointegration of the viral genome, and might be included in virions at the ration of zero to 3 BAF dimer per virion. The myristoylation signal and the NLS thus exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles (By similarity).<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref>	+	[https://www.uniprot.org/uniprot/POL_HV1H2 POL_HV1H2] Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to play a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. It binds in the cytoplasm the human BAF protein which prevent autointegration of the viral genome, and might be included in virions at the ration of zero to 3 BAF dimer per virion. The myristoylation signal and the NLS thus exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles (By similarity).<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 22:		Line 20:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1c1c ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1c1c ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Two analogues of the nonnucleoside inhibitor of HIV-1 RT, MKC-442 (emivirine), containing different C6 substituents have been designed to be less susceptible to the commonly found drug-resistance mutation of Tyr181Cys. Compound TNK-6123 had a C6 thiocyclohexyl group designed to have more flexibility in adapting to the mutated drug-binding site. GCA-186 had additional 3',5'-dimethyl substituents aimed at forming close contacts with the conserved residue Trp229. Both compounds showed approximately 30-fold greater inhibitory effect than MKC-442 to the Tyr181Cys mutant virus as well as to the clinically important Lys103Asn virus. X-ray crystallographic structure determination of complexes with HIV-1 RT confirmed the predicted binding modes. These strategies might be used to improve the resilience of other NNRTI series against common drug-resistance mutations.
-
-	Design of MKC-442 (emivirine) analogues with improved activity against drug-resistant HIV mutants.,Hopkins AL, Ren J, Tanaka H, Baba M, Okamato M, Stuart DI, Stammers DK J Med Chem. 1999 Nov 4;42(22):4500-5. PMID:10579814<ref>PMID:10579814</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1c1c" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 38:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human immunodeficiency virus 1]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: RNA-directed DNA polymerase]]~~	+	[[Category: Baba M]]
-	[[Category: Baba, M]]	+	[[Category: Hopkins AL]]
-	[[Category: Hopkins~~, A L~~]]	+	[[Category: Okamato M]]
-	[[Category: Okamato, M]]	+	[[Category: Ren J]]
-	[[Category: Ren, J]]	+	[[Category: Stammers DK]]
-	[[Category: Stammers~~, D K~~]]	+	[[Category: Stuart DI]]
-	[[Category: Stuart~~, D I~~]]	+	[[Category: Tanaka H]]
-	[[Category: Tanaka, H]]	+
-	~~[[Category: Aid]]~~	+
-	~~[[Category: Drug design]]~~	+
-	~~[[Category: Hiv-1 reverse transcriptase]]~~	+
-	~~[[Category: Non-nucleoside inhibitor]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 10:32, 14 July 2021

OCA — Wed, 14 Jul 2021 10:32:16 GMT

←Older revision		Revision as of 10:32, 14 July 2021
Line 3:		Line 3:
	<StructureSection load='1c1c' size='340' side='right'caption='[[1c1c]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='1c1c' size='340' side='right'caption='[[1c1c]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1c1c]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C1C OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1C1C FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1c1c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C1C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C1C FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=612:6-(CYCLOHEXYLSULFANYL)-1-(ETHOXYMETHYL)-5-(1-METHYLETHYL)PYRIMIDINE-2,4(1H,3H)-DIONE'>612</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=612:6-(CYCLOHEXYLSULFANYL)-1-(ETHOXYMETHYL)-5-(1-METHYLETHYL)PYRIMIDINE-2,4(1H,3H)-DIONE'>612</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1rtv\|1rtv]], [[1rth\|1rth]], [[1vru\|1vru]], [[1rti\|1rti]], [[1rtj\|1rtj]], [[1rev\|1rev]], [[1rt1\|1rt1]], [[1rt2\|1rt2]], [[1klm\|1klm]], [[1rt3\|1rt3]], [[1rt4\|1rt4]], [[1rt5\|1rt5]], [[1rt6\|1rt6]], [[1rt7\|1rt7]], [[1c0t\|1c0t]], [[1c0u\|1c0u]], [[1c1b\|1c1b]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1rtv\|1rtv]], [[1rth\|1rth]], [[1vru\|1vru]], [[1rti\|1rti]], [[1rtj\|1rtj]], [[1rev\|1rev]], [[1rt1\|1rt1]], [[1rt2\|1rt2]], [[1klm\|1klm]], [[1rt3\|1rt3]], [[1rt4\|1rt4]], [[1rt5\|1rt5]], [[1rt6\|1rt6]], [[1rt7\|1rt7]], [[1c0t\|1c0t]], [[1c0u\|1c0u]], [[1c1b\|1c1b]]</div></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1c1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c1c OCA], [~~http~~://pdbe.org/1c1c PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1c1c RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1c1c PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1c1c ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1c1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c1c OCA], [https://pdbe.org/1c1c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c1c RCSB], [https://www.ebi.ac.uk/pdbsum/1c1c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c1c ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/POL_HV1H2 POL_HV1H2]] Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to play a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. It binds in the cytoplasm the human BAF protein which prevent autointegration of the viral genome, and might be included in virions at the ration of zero to 3 BAF dimer per virion. The myristoylation signal and the NLS thus exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles (By similarity).<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref>	+	[[https://www.uniprot.org/uniprot/POL_HV1H2 POL_HV1H2]] Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to play a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. It binds in the cytoplasm the human BAF protein which prevent autointegration of the viral genome, and might be included in virions at the ration of zero to 3 BAF dimer per virion. The myristoylation signal and the NLS thus exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles (By similarity).<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 33:		Line 33:

	==See Also==		==See Also==
-	*[[Reverse transcriptase\|Reverse transcriptase]]	+	*[[Reverse transcriptase 3D structures\|Reverse transcriptase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:26, 10 October 2019

OCA — Thu, 10 Oct 2019 07:26:04 GMT

←Older revision		Revision as of 07:26, 10 October 2019
Line 1:		Line 1:

	==CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH TNK-6123==		==CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH TNK-6123==
-	<StructureSection load='1c1c' size='340' side='right' caption='[[1c1c]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='1c1c' size='340' side='right'caption='[[1c1c]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1c1c]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C1C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1C1C FirstGlance]. <br>		<table><tr><td colspan='2'>[[1c1c]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C1C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1C1C FirstGlance]. <br>
Line 16:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c1/1c1c_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c1/1c1c_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 31:		Line 31:
	</div>		</div>
	<div class="pdbe-citations 1c1c" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1c1c" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Reverse transcriptase\|Reverse transcriptase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: RNA-directed DNA polymerase]]		[[Category: RNA-directed DNA polymerase]]
	[[Category: Baba, M]]		[[Category: Baba, M]]

OCA at 08:17, 29 November 2017

OCA — Wed, 29 Nov 2017 08:17:31 GMT

←Older revision		Revision as of 08:17, 29 November 2017
Line 1:		Line 1:
		+
	==CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH TNK-6123==		==CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH TNK-6123==
	<StructureSection load='1c1c' size='340' side='right' caption='[[1c1c]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='1c1c' size='340' side='right' caption='[[1c1c]], [[Resolution\|resolution]] 2.50Å' scene=''>
Line 7:		Line 8:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1rtv\|1rtv]], [[1rth\|1rth]], [[1vru\|1vru]], [[1rti\|1rti]], [[1rtj\|1rtj]], [[1rev\|1rev]], [[1rt1\|1rt1]], [[1rt2\|1rt2]], [[1klm\|1klm]], [[1rt3\|1rt3]], [[1rt4\|1rt4]], [[1rt5\|1rt5]], [[1rt6\|1rt6]], [[1rt7\|1rt7]], [[1c0t\|1c0t]], [[1c0u\|1c0u]], [[1c1b\|1c1b]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1rtv\|1rtv]], [[1rth\|1rth]], [[1vru\|1vru]], [[1rti\|1rti]], [[1rtj\|1rtj]], [[1rev\|1rev]], [[1rt1\|1rt1]], [[1rt2\|1rt2]], [[1klm\|1klm]], [[1rt3\|1rt3]], [[1rt4\|1rt4]], [[1rt5\|1rt5]], [[1rt6\|1rt6]], [[1rt7\|1rt7]], [[1c0t\|1c0t]], [[1c0u\|1c0u]], [[1c1b\|1c1b]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1c1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c1c OCA], [http://pdbe.org/1c1c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1c1c RCSB], [http://www.ebi.ac.uk/pdbsum/1c1c PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1c1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c1c OCA], [http://pdbe.org/1c1c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1c1c RCSB], [http://www.ebi.ac.uk/pdbsum/1c1c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1c1c ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 30:		Line 31:
	</div>		</div>
	<div class="pdbe-citations 1c1c" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1c1c" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Reverse transcriptase\|Reverse transcriptase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 22:35, 8 February 2016

OCA — Mon, 08 Feb 2016 22:35:36 GMT

←Older revision		Revision as of 22:35, 8 February 2016
Line 19:		Line 19:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1c1c ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 16:00, 10 September 2015

OCA — Thu, 10 Sep 2015 16:00:20 GMT

←Older revision		Revision as of 16:00, 10 September 2015
Line 7:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1rtv\|1rtv]], [[1rth\|1rth]], [[1vru\|1vru]], [[1rti\|1rti]], [[1rtj\|1rtj]], [[1rev\|1rev]], [[1rt1\|1rt1]], [[1rt2\|1rt2]], [[1klm\|1klm]], [[1rt3\|1rt3]], [[1rt4\|1rt4]], [[1rt5\|1rt5]], [[1rt6\|1rt6]], [[1rt7\|1rt7]], [[1c0t\|1c0t]], [[1c0u\|1c0u]], [[1c1b\|1c1b]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1rtv\|1rtv]], [[1rth\|1rth]], [[1vru\|1vru]], [[1rti\|1rti]], [[1rtj\|1rtj]], [[1rev\|1rev]], [[1rt1\|1rt1]], [[1rt2\|1rt2]], [[1klm\|1klm]], [[1rt3\|1rt3]], [[1rt4\|1rt4]], [[1rt5\|1rt5]], [[1rt6\|1rt6]], [[1rt7\|1rt7]], [[1c0t\|1c0t]], [[1c0u\|1c0u]], [[1c1b\|1c1b]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1c1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c1c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1c1c RCSB], [http://www.ebi.ac.uk/pdbsum/1c1c PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1c1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c1c OCA], [http://pdbe.org/1c1c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1c1c RCSB], [http://www.ebi.ac.uk/pdbsum/1c1c PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 29:		Line 29:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 1c1c" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 02:36, 25 December 2014

OCA — Thu, 25 Dec 2014 02:36:03 GMT

←Older revision		Revision as of 02:36, 25 December 2014
Line 9:		Line 9:
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1c1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c1c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1c1c RCSB], [http://www.ebi.ac.uk/pdbsum/1c1c PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1c1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c1c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1c1c RCSB], [http://www.ebi.ac.uk/pdbsum/1c1c PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/POL_HV1H2 POL_HV1H2]] Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to play a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. It binds in the cytoplasm the human BAF protein which prevent autointegration of the viral genome, and might be included in virions at the ration of zero to 3 BAF dimer per virion. The myristoylation signal and the NLS thus exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles (By similarity).<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 00:44, 23 December 2014

OCA — Tue, 23 Dec 2014 00:44:07 GMT

←Older revision		Revision as of 00:44, 23 December 2014
Line 2:		Line 2:
	<StructureSection load='1c1c' size='340' side='right' caption='[[1c1c]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='1c1c' size='340' side='right' caption='[[1c1c]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1c1c]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C1C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1C1C FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1c1c]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C1C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1C1C FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=612:6-(CYCLOHEXYLSULFANYL)-1-(ETHOXYMETHYL)-5-(1-METHYLETHYL)PYRIMIDINE-2,4(1H,3H)-DIONE'>612</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=612:6-(CYCLOHEXYLSULFANYL)-1-(ETHOXYMETHYL)-5-(1-METHYLETHYL)PYRIMIDINE-2,4(1H,3H)-DIONE'>612</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr>

OCA at 07:06, 12 November 2014

OCA — Wed, 12 Nov 2014 07:06:51 GMT

←Older revision		Revision as of 07:06, 12 November 2014
Line 2:		Line 2:
	<StructureSection load='1c1c' size='340' side='right' caption='[[1c1c]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='1c1c' size='340' side='right' caption='[[1c1c]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1c1c]] is a 2 chain structure ~~with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]~~. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C1C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1C1C FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1c1c]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C1C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1C1C FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=612:6-(CYCLOHEXYLSULFANYL)-1-(ETHOXYMETHYL)-5-(1-METHYLETHYL)PYRIMIDINE-2,4(1H,3H)-DIONE'>612</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=612:6-(CYCLOHEXYLSULFANYL)-1-(ETHOXYMETHYL)-5-(1-METHYLETHYL)PYRIMIDINE-2,4(1H,3H)-DIONE'>612</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=~~CSW~~:~~CYSTEINE~~-~~S-DIOXIDE~~'>~~CSW~~</scene></td></tr>	+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1rtv\|1rtv]], [[1rth\|1rth]], [[1vru\|1vru]], [[1rti\|1rti]], [[1rtj\|1rtj]], [[1rev\|1rev]], [[1rt1\|1rt1]], [[1rt2\|1rt2]], [[1klm\|1klm]], [[1rt3\|1rt3]], [[1rt4\|1rt4]], [[1rt5\|1rt5]], [[1rt6\|1rt6]], [[1rt7\|1rt7]], [[1c0t\|1c0t]], [[1c0u\|1c0u]], [[1c1b\|1c1b]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1rtv\|1rtv]], [[1rth\|1rth]], [[1vru\|1vru]], [[1rti\|1rti]], [[1rtj\|1rtj]], [[1rev\|1rev]], [[1rt1\|1rt1]], [[1rt2\|1rt2]], [[1klm\|1klm]], [[1rt3\|1rt3]], [[1rt4\|1rt4]], [[1rt5\|1rt5]], [[1rt6\|1rt6]], [[1rt7\|1rt7]], [[1c0t\|1c0t]], [[1c0u\|1c0u]], [[1c1b\|1c1b]]</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] </span></td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1c1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c1c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1c1c RCSB], [http://www.ebi.ac.uk/pdbsum/1c1c PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1c1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c1c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1c1c RCSB], [http://www.ebi.ac.uk/pdbsum/1c1c PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 34:		Line 34:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Human immunodeficiency virus 1]]
	[[Category: RNA-directed DNA polymerase]]		[[Category: RNA-directed DNA polymerase]]
-	[[Category: Baba, M.]]	+	[[Category: Baba, M]]
-	[[Category: Hopkins, A L.]]	+	[[Category: Hopkins, A L]]
-	[[Category: Okamato, M.]]	+	[[Category: Okamato, M]]
-	[[Category: Ren, J.]]	+	[[Category: Ren, J]]
-	[[Category: Stammers, D K.]]	+	[[Category: Stammers, D K]]
-	[[Category: Stuart, D I.]]	+	[[Category: Stuart, D I]]
-	[[Category: Tanaka, H.]]	+	[[Category: Tanaka, H]]
	[[Category: Aid]]		[[Category: Aid]]
	[[Category: Drug design]]		[[Category: Drug design]]

OCA at 17:11, 20 August 2014

OCA — Wed, 20 Aug 2014 17:11:59 GMT

←Older revision		Revision as of 17:11, 20 August 2014
Line 1:		Line 1:
-	[[~~Image:~~1c1c.~~png~~\|~~left~~\|200px]]	+	==CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH TNK-6123==
		+	<StructureSection load='1c1c' size='340' side='right' caption='[[1c1c]], [[Resolution\|resolution]] 2.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1c1c]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C1C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1C1C FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=612:6-(CYCLOHEXYLSULFANYL)-1-(ETHOXYMETHYL)-5-(1-METHYLETHYL)PYRIMIDINE-2,4(1H,3H)-DIONE'>612</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSW:CYSTEINE-S-DIOXIDE'>CSW</scene></td></tr>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1rtv\|1rtv]], [[1rth\|1rth]], [[1vru\|1vru]], [[1rti\|1rti]], [[1rtj\|1rtj]], [[1rev\|1rev]], [[1rt1\|1rt1]], [[1rt2\|1rt2]], [[1klm\|1klm]], [[1rt3\|1rt3]], [[1rt4\|1rt4]], [[1rt5\|1rt5]], [[1rt6\|1rt6]], [[1rt7\|1rt7]], [[1c0t\|1c0t]], [[1c0u\|1c0u]], [[1c1b\|1c1b]]</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] </span></td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1c1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c1c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1c1c RCSB], [http://www.ebi.ac.uk/pdbsum/1c1c PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c1/1c1c_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Two analogues of the nonnucleoside inhibitor of HIV-1 RT, MKC-442 (emivirine), containing different C6 substituents have been designed to be less susceptible to the commonly found drug-resistance mutation of Tyr181Cys. Compound TNK-6123 had a C6 thiocyclohexyl group designed to have more flexibility in adapting to the mutated drug-binding site. GCA-186 had additional 3',5'-dimethyl substituents aimed at forming close contacts with the conserved residue Trp229. Both compounds showed approximately 30-fold greater inhibitory effect than MKC-442 to the Tyr181Cys mutant virus as well as to the clinically important Lys103Asn virus. X-ray crystallographic structure determination of complexes with HIV-1 RT confirmed the predicted binding modes. These strategies might be used to improve the resilience of other NNRTI series against common drug-resistance mutations.

-	~~{{STRUCTURE_1c1c\| PDB=1c1c \| SCENE= }}~~	+	Design of MKC-442 (emivirine) analogues with improved activity against drug-resistant HIV mutants.,Hopkins AL, Ren J, Tanaka H, Baba M, Okamato M, Stuart DI, Stammers DK J Med Chem. 1999 Nov 4;42(22):4500-5. PMID:10579814<ref>PMID:10579814</ref>

-	~~===CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH TNK-6123===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_10579814}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[1c1c]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=1C1C OCA].~~	+

	==See Also==		==See Also==
	*[[Reverse transcriptase\|Reverse transcriptase]]		*[[Reverse transcriptase\|Reverse transcriptase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:010579814<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]
	[[Category: RNA-directed DNA polymerase]]		[[Category: RNA-directed DNA polymerase]]