1klm - Revision history

OCA at 06:05, 3 April 2024

OCA — Wed, 03 Apr 2024 06:05:36 GMT

←Older revision		Revision as of 06:05, 3 April 2024
Line 3:		Line 3:
	<StructureSection load='1klm' size='340' side='right'caption='[[1klm]], [[Resolution\|resolution]] 2.65Å' scene=''>		<StructureSection load='1klm' size='340' side='right'caption='[[1klm]], [[Resolution\|resolution]] 2.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1klm]] 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=1KLM OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=1KLM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1klm]] 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=1KLM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KLM FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=SPP:(1-(5-METHANSULPHONAMIDO-1H-INDOL-2-YL-CARBONYL)4~~-[~~METHYLAMINO)PYRIDINYL~~]~~PIPERAZINE'>SPP</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]] 2.65Å</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=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=SPP:(1-(5-METHANSULPHONAMIDO-1H-INDOL-2-YL-CARBONYL)4-[METHYLAMINO)PYRIDINYL]PIPERAZINE'>SPP</scene></td></tr>
-	~~<tr id~~='~~gene'><td class~~=~~"sblockLbl"><b>[[Gene\|Gene~~:~~]]</b></td><td class="sblockDat">POL~~ (~~[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=~~5~~&id=11676 9HIV1])</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=1klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1klm OCA], [https://pdbe.org/1klm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1klm RCSB], [https://www.ebi.ac.uk/pdbsum/1klm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1klm ProSAT]</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~~://proteopedia.org/fgij/fg.htm?mol=1klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1klm OCA], [~~http~~://pdbe.org/1klm PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1klm RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1klm PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1klm 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 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=1klm 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=1klm ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The viral reverse transcriptase (RT) provides an attractive target in the search for anti-HIV therapies. The nonnucleoside inhibitors (NNIs) are a diverse set of compounds (usually HIV-1 specific) that function by distorting the polymerase active site upon binding in a nearby pocket. Despite being potent and of generally low toxicity, their clinical use has been limited by rapid selection for resistant viral populations. The 2.65-A resolution structure of the complex between HIV-1 RT and the bis(heteroaryl)piperazine (BHAP) NNI, 1-(5-methanesulfonamido-1H-indol-2-yl-carbonyl)-4- [3-(1-methyl-ethylamino) pyridinyl] piperazine (U-90152), reveals the inhibitor conformation and bound water molecules. The bulky U-90152 molecule occupies the same pocket as other NNIs, but the complex is stabilized quite differently, in particular by hydrogen bonding to the main chain of Lys-103 and extensive hydrophobic contacts with Pro-236. These interactions rationalize observed resistance mutations, notably Pro-236-Leu, which occurs characteristically for BHAPs. When bound, part of U-90152 protrudes into the solvent creating a channel between Pro-236 and the polypeptide segments 225-226 and 105-106, giving the first clear evidence of the entry mode for NNIs. The structure allows prediction of binding modes for related inhibitors [(altrylamino)piperidine-BHAPs] and suggests changes to U-90152, such as the addition of a 6 amino group to the pyridine ring, which may make binding more resilient to mutations in the RT. The observation of novel hydrogen bonding to the protein main chain may provide lessons for the improvement of quite different inhibitors.
-
-	Unique features in the structure of the complex between HIV-1 reverse transcriptase and the bis(heteroaryl)piperazine (BHAP) U-90152 explain resistance mutations for this nonnucleoside inhibitor.,Esnouf RM, Ren J, Hopkins AL, Ross CK, Jones EY, Stammers DK, Stuart DI Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3984-9. PMID:9108091<ref>PMID:9108091</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1klm" 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: Esnouf RM]]
-	[[Category: Esnouf~~, R M~~]]	+	[[Category: Ren J]]
-	[[Category: Ren, J]]	+	[[Category: Stammers DK]]
-	[[Category: Stammers~~, D K~~]]	+	[[Category: Stuart DI]]
-	[[Category: Stuart~~, D I]]~~	+
-	~~[[Category: Aid]]~~	+
-	~~[[Category: Bhap u-90152]]~~	+
-	~~[[Category: Drug]]~~	+
-	~~[[Category: Endonuclease]]~~	+
-	~~[[Category: Hiv-1]]~~	+
-	~~[[Category: Hiv-1 reverse transcriptase]]~~	+
-	~~[[Category: Nucleotidyltransferase]]~~	+
-	~~[[Category: Rna-directed dna polymerase~~]]	+

OCA at 07:46, 25 November 2020

OCA — Wed, 25 Nov 2020 07:46:43 GMT

←Older revision		Revision as of 07:46, 25 November 2020
Line 1:		Line 1:

	==HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH BHAP U-90152==		==HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH BHAP U-90152==
-	<StructureSection load='1klm' size='340' side='right' caption='[[1klm]], [[Resolution\|resolution]] 2.65Å' scene=''>	+	<StructureSection load='1klm' size='340' side='right'caption='[[1klm]], [[Resolution\|resolution]] 2.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1klm]] 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=1KLM OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1KLM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1klm]] 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=1KLM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1KLM FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SPP:(1-(5-METHANSULPHONAMIDO-1H-INDOL-2-YL-CARBONYL)4-[METHYLAMINO)PYRIDINYL]PIPERAZINE'>SPP</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SPP:(1-(5-METHANSULPHONAMIDO-1H-INDOL-2-YL-CARBONYL)4-[METHYLAMINO)PYRIDINYL]PIPERAZINE'>SPP</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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</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=1klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1klm OCA], [http://pdbe.org/1klm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1klm RCSB], [http://www.ebi.ac.uk/pdbsum/1klm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1klm ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1klm OCA], [http://pdbe.org/1klm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1klm RCSB], [http://www.ebi.ac.uk/pdbsum/1klm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1klm ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 31:		Line 31:
	</div>		</div>
	<div class="pdbe-citations 1klm" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1klm" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Reverse transcriptase 3D structures\|Reverse transcriptase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: RNA-directed DNA polymerase]]		[[Category: RNA-directed DNA polymerase]]
	[[Category: Esnouf, R M]]		[[Category: Esnouf, R M]]

OCA at 21:11, 24 January 2018

OCA — Wed, 24 Jan 2018 21:11:59 GMT

←Older revision		Revision as of 21:11, 24 January 2018
Line 1:		Line 1:
		+
	==HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH BHAP U-90152==		==HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH BHAP U-90152==
	<StructureSection load='1klm' size='340' side='right' caption='[[1klm]], [[Resolution\|resolution]] 2.65Å' scene=''>		<StructureSection load='1klm' size='340' side='right' caption='[[1klm]], [[Resolution\|resolution]] 2.65Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</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=1klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1klm OCA], [http://pdbe.org/1klm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1klm RCSB], [http://www.ebi.ac.uk/pdbsum/1klm 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=1klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1klm OCA], [http://pdbe.org/1klm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1klm RCSB], [http://www.ebi.ac.uk/pdbsum/1klm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1klm ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 15:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kl/1klm_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kl/1klm_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 30:		Line 31:
	</div>		</div>
	<div class="pdbe-citations 1klm" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1klm" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Reverse transcriptase\|Reverse transcriptase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:36, 9 February 2016

OCA — Tue, 09 Feb 2016 10:36:38 GMT

←Older revision		Revision as of 10:36, 9 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=1klm ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 21:27, 10 September 2015

OCA — Thu, 10 Sep 2015 21:27:05 GMT

←Older revision		Revision as of 21:27, 10 September 2015
Line 2:		Line 2:
	<StructureSection load='1klm' size='340' side='right' caption='[[1klm]], [[Resolution\|resolution]] 2.65Å' scene=''>		<StructureSection load='1klm' size='340' side='right' caption='[[1klm]], [[Resolution\|resolution]] 2.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1klm]] 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=1KLM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KLM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1klm]] 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=1KLM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KLM FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SPP:(1-(5-METHANSULPHONAMIDO-1H-INDOL-2-YL-CARBONYL)4-[METHYLAMINO)PYRIDINYL]PIPERAZINE'>SPP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SPP:(1-(5-METHANSULPHONAMIDO-1H-INDOL-2-YL-CARBONYL)4-[METHYLAMINO)PYRIDINYL]PIPERAZINE'>SPP</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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 ~~Human immunodeficiency virus 1~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</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=1klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1klm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1klm RCSB], [http://www.ebi.ac.uk/pdbsum/1klm 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=1klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1klm OCA], [http://pdbe.org/1klm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1klm RCSB], [http://www.ebi.ac.uk/pdbsum/1klm 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 1klm" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 36:		Line 37:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Human immunodeficiency virus 1]]
	[[Category: RNA-directed DNA polymerase]]		[[Category: RNA-directed DNA polymerase]]
	[[Category: Esnouf, R M]]		[[Category: Esnouf, R M]]

OCA at 06:18, 25 December 2014

OCA — Thu, 25 Dec 2014 06:18:57 GMT

←Older revision		Revision as of 06:18, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1klm]] 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=1KLM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KLM FirstGlance]. <br>		<table><tr><td colspan='2'>[[1klm]] 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=1KLM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KLM FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SPP:(1-(5-METHANSULPHONAMIDO-1H-INDOL-2-YL-CARBONYL)4-[METHYLAMINO)PYRIDINYL]PIPERAZINE'>SPP</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SPP:(1-(5-METHANSULPHONAMIDO-1H-INDOL-2-YL-CARBONYL)4-[METHYLAMINO)PYRIDINYL]PIPERAZINE'>SPP</scene></td></tr>
-	<tr><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><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1])</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=1klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1klm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1klm RCSB], [http://www.ebi.ac.uk/pdbsum/1klm 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=1klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1klm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1klm RCSB], [http://www.ebi.ac.uk/pdbsum/1klm 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]]
Line 36:		Line 38:
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]
	[[Category: RNA-directed DNA polymerase]]		[[Category: RNA-directed DNA polymerase]]
-	[[Category: Esnouf, R M.]]	+	[[Category: Esnouf, R M]]
-	[[Category: Ren, J.]]	+	[[Category: Ren, J]]
-	[[Category: Stammers, D K.]]	+	[[Category: Stammers, D K]]
-	[[Category: Stuart, D I.]]	+	[[Category: Stuart, D I]]
	[[Category: Aid]]		[[Category: Aid]]
	[[Category: Bhap u-90152]]		[[Category: Bhap u-90152]]

OCA at 13:53, 28 September 2014

OCA — Sun, 28 Sep 2014 13:53:32 GMT

←Older revision		Revision as of 13:53, 28 September 2014
Line 1:		Line 1:
-	[[~~Image:~~1klm.~~png~~\|~~left~~\|200px]]	+	==HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH BHAP U-90152==
		+	<StructureSection load='1klm' size='340' side='right' caption='[[1klm]], [[Resolution\|resolution]] 2.65Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1klm]] 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=1KLM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KLM FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SPP:(1-(5-METHANSULPHONAMIDO-1H-INDOL-2-YL-CARBONYL)4-[METHYLAMINO)PYRIDINYL]PIPERAZINE'>SPP</scene><br>
		+	<tr><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>[[Gene\|Gene:]]</b></td><td class="sblockDat">POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1])</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=1klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1klm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1klm RCSB], [http://www.ebi.ac.uk/pdbsum/1klm 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/kl/1klm_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 ==
		+	The viral reverse transcriptase (RT) provides an attractive target in the search for anti-HIV therapies. The nonnucleoside inhibitors (NNIs) are a diverse set of compounds (usually HIV-1 specific) that function by distorting the polymerase active site upon binding in a nearby pocket. Despite being potent and of generally low toxicity, their clinical use has been limited by rapid selection for resistant viral populations. The 2.65-A resolution structure of the complex between HIV-1 RT and the bis(heteroaryl)piperazine (BHAP) NNI, 1-(5-methanesulfonamido-1H-indol-2-yl-carbonyl)-4- [3-(1-methyl-ethylamino) pyridinyl] piperazine (U-90152), reveals the inhibitor conformation and bound water molecules. The bulky U-90152 molecule occupies the same pocket as other NNIs, but the complex is stabilized quite differently, in particular by hydrogen bonding to the main chain of Lys-103 and extensive hydrophobic contacts with Pro-236. These interactions rationalize observed resistance mutations, notably Pro-236-Leu, which occurs characteristically for BHAPs. When bound, part of U-90152 protrudes into the solvent creating a channel between Pro-236 and the polypeptide segments 225-226 and 105-106, giving the first clear evidence of the entry mode for NNIs. The structure allows prediction of binding modes for related inhibitors [(altrylamino)piperidine-BHAPs] and suggests changes to U-90152, such as the addition of a 6 amino group to the pyridine ring, which may make binding more resilient to mutations in the RT. The observation of novel hydrogen bonding to the protein main chain may provide lessons for the improvement of quite different inhibitors.

-	~~{{STRUCTURE_1klm\| PDB=1klm \| SCENE= }}~~	+	Unique features in the structure of the complex between HIV-1 reverse transcriptase and the bis(heteroaryl)piperazine (BHAP) U-90152 explain resistance mutations for this nonnucleoside inhibitor.,Esnouf RM, Ren J, Hopkins AL, Ross CK, Jones EY, Stammers DK, Stuart DI Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3984-9. PMID:9108091<ref>PMID:9108091</ref>

-	~~===HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH BHAP~~ U~~-90152===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_9108091}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[1klm]] 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=1KLM OCA].~~	+

	==See Also==		==See Also==
	*[[Reverse transcriptase\|Reverse transcriptase]]		*[[Reverse transcriptase\|Reverse transcriptase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:009108091<~~/~~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]]

OCA at 13:35, 20 October 2012

OCA — Sat, 20 Oct 2012 13:35:59 GMT

←Older revision		Revision as of 13:35, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[1klm]] is a 2 chain structure ~~of [[Reverse transcriptase]]~~ 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=1KLM OCA].	+	[[1klm]] 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=1KLM OCA].

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

OCA: Protected "1klm" [edit=sysop:move=sysop]

OCA — Wed, 18 Jul 2012 04:29:47 GMT

Protected "1klm" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:29, 18 July 2012

OCA at 04:29, 18 July 2012

OCA — Wed, 18 Jul 2012 04:29:46 GMT

←Older revision		Revision as of 04:29, 18 July 2012
Line 1:		Line 1:
-	{{Seed}}
	[[Image:1klm.png\|left\|200px]]		[[Image:1klm.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_1klm", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_1klm\| PDB=1klm \| SCENE= }}		{{STRUCTURE_1klm\| PDB=1klm \| SCENE= }}

	===HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH BHAP U-90152===		===HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH BHAP U-90152===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_9108091}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 9108091 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_9108091}}		{{ABSTRACT_PUBMED_9108091}}

	==About this Structure==		==About this Structure==
-	~~1KLM~~ is a 2 ~~chains~~ structure of ~~sequences~~ 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=1KLM OCA].	+	[[1klm]] is a 2 chain structure of [[Reverse transcriptase]] 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=1KLM OCA].
		+
		+	==See Also==
		+	*[[Reverse transcriptase\|Reverse transcriptase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~9108091~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:009108091</ref><references group="xtra"/>
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]
	[[Category: RNA-directed DNA polymerase]]		[[Category: RNA-directed DNA polymerase]]
Line 38:		Line 29:
	[[Category: Nucleotidyltransferase]]		[[Category: Nucleotidyltransferase]]
	[[Category: Rna-directed dna polymerase]]		[[Category: Rna-directed dna polymerase]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 09:11:43 2009''