2zga - Revision history

OCA at 13:35, 1 November 2023

OCA — Wed, 01 Nov 2023 13:35:34 GMT

←Older revision		Revision as of 13:35, 1 November 2023
Line 3:		Line 3:
	<StructureSection load='2zga' size='340' side='right'caption='[[2zga]], [[Resolution\|resolution]] 1.65Å' scene=''>		<StructureSection load='2zga' size='340' side='right'caption='[[2zga]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2zga]] is a 1 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=2ZGA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZGA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2zga]] is a 1 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=2ZGA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZGA FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=YDP:(3S,4S),~~-3,~~4-BIS-~~[~~(4-CARBAMOYL-BENZENSULFONYL)-(3-METHYL-BUT-2-ENYL)-AMINO~~]~~-PYRROLIDINE'>YDP</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]] 1.65Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>gag-pol ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id~~=11676 9HIV1])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=YDP:(3S,4S),-3,4-BIS-[(4-CARBAMOYL-BENZENSULFONYL)-(3-METHYL-BUT-2-ENYL)-AMINO]-PYRROLIDINE'>YDP</scene></td></tr>
-	~~<tr id='activity'><td class~~="~~sblockLbl~~"><~~b>Activity:</b></td><td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[https~~:~~//en.wikipedia.org/wiki/HIV~~-~~1_retropepsin HIV~~-~~1 retropepsin], with EC number~~ [~~https://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=~~3~~.4.23.16 3.4.23.16~~] </~~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=2zga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zga OCA], [https://pdbe.org/2zga PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zga RCSB], [https://www.ebi.ac.uk/pdbsum/2zga PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zga 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=2zga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zga OCA], [https://pdbe.org/2zga PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zga RCSB], [https://www.ebi.ac.uk/pdbsum/2zga PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zga ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/POL_HV1BR POL_HV1BR]] 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). 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). 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 (By similarity). 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 (By similarity).	+	[https://www.uniprot.org/uniprot/POL_HV1BR POL_HV1BR] 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). 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). 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 (By similarity). 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 (By similarity).
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 37:		Line 36:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~HIV-~~1 ~~retropepsin~~]]	+	[[Category: Human immunodeficiency virus 1]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Blum, A]]	+	[[Category: Blum A]]
-	[[Category: Boettcher, J]]	+	[[Category: Boettcher J]]
-	[[Category: Diederich~~, W E~~]]	+	[[Category: Diederich WE]]
-	[[Category: Heine, A]]	+	[[Category: Heine A]]
-	[[Category: Klebe, G]]	+	[[Category: Klebe G]]
-	~~[[Category: Hydrolase-hydrolase inhibitor complex~~]]	+

OCA at 17:29, 15 December 2021

OCA — Wed, 15 Dec 2021 17:29:35 GMT

←Older revision		Revision as of 17:29, 15 December 2021
Line 1:		Line 1:

	==HIV-1 protease in complex with a dimethylallyl decorated pyrrolidine based inhibitor (hexagonal space group)==		==HIV-1 protease in complex with a dimethylallyl decorated pyrrolidine based inhibitor (hexagonal space group)==
-	<StructureSection load='2zga' size='340' side='right' caption='[[2zga]], [[Resolution\|resolution]] 1.65Å' scene=''>	+	<StructureSection load='2zga' size='340' side='right'caption='[[2zga]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2zga]] is a 1 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=2ZGA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2ZGA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2zga]] is a 1 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=2ZGA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZGA FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YDP:(3S,4S),-3,4-BIS-[(4-CARBAMOYL-BENZENSULFONYL)-(3-METHYL-BUT-2-ENYL)-AMINO]-PYRROLIDINE'>YDP</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=YDP:(3S,4S),-3,4-BIS-[(4-CARBAMOYL-BENZENSULFONYL)-(3-METHYL-BUT-2-ENYL)-AMINO]-PYRROLIDINE'>YDP</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-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">gag-pol ([https://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/HIV-1_retropepsin HIV-1 retropepsin], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </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=2zga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zga OCA], [~~http~~://pdbe.org/2zga PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2zga RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2zga PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2zga 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=2zga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zga OCA], [https://pdbe.org/2zga PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zga RCSB], [https://www.ebi.ac.uk/pdbsum/2zga PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zga ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/POL_HV1BR POL_HV1BR]] 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). 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). 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 (By similarity). 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 (By similarity).	+	[[https://www.uniprot.org/uniprot/POL_HV1BR POL_HV1BR]] 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). 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). 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 (By similarity). 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 (By similarity).
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 32:		Line 32:

	==See Also==		==See Also==
-	*[[Immunodeficiency virus protease\|Immunodeficiency virus protease]]	+	*[[Immunodeficiency virus protease 3D structures\|Immunodeficiency virus protease 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 38:		Line 38:
	</StructureSection>		</StructureSection>
	[[Category: HIV-1 retropepsin]]		[[Category: HIV-1 retropepsin]]
		+	[[Category: Large Structures]]
	[[Category: Blum, A]]		[[Category: Blum, A]]
	[[Category: Boettcher, J]]		[[Category: Boettcher, J]]

OCA at 06:48, 18 October 2018

OCA — Thu, 18 Oct 2018 06:48:18 GMT

←Older revision		Revision as of 06:48, 18 October 2018
Line 15:		Line 15:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zg/2zga_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zg/2zga_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 30:
	</div>		</div>
	<div class="pdbe-citations 2zga" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 2zga" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Immunodeficiency virus protease\|Immunodeficiency virus protease]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 21:09, 4 August 2016

OCA — Thu, 04 Aug 2016 21:09:56 GMT

←Older revision		Revision as of 21:09, 4 August 2016
Line 1:		Line 1:
		+
	==HIV-1 protease in complex with a dimethylallyl decorated pyrrolidine based inhibitor (hexagonal space group)==		==HIV-1 protease in complex with a dimethylallyl decorated pyrrolidine based inhibitor (hexagonal space group)==
	<StructureSection load='2zga' size='340' side='right' caption='[[2zga]], [[Resolution\|resolution]] 1.65Å' scene=''>		<StructureSection load='2zga' size='340' side='right' caption='[[2zga]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2zga]] is a 1 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=2ZGA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZGA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2zga]] is a 1 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=2ZGA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZGA FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YDP:(3S,4S),-3,4-BIS-[(4-CARBAMOYL-BENZENSULFONYL)-(3-METHYL-BUT-2-ENYL)-AMINO]-PYRROLIDINE'>YDP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YDP:(3S,4S),-3,4-BIS-[(4-CARBAMOYL-BENZENSULFONYL)-(3-METHYL-BUT-2-ENYL)-AMINO]-PYRROLIDINE'>YDP</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-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">gag-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/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </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=2zga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zga OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zga RCSB], [http://www.ebi.ac.uk/pdbsum/2zga 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=2zga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zga OCA], [http://pdbe.org/2zga PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zga RCSB], [http://www.ebi.ac.uk/pdbsum/2zga PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zga ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		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=2zga ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 28:		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 2zga" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
Line 33:		Line 35:
	</StructureSection>		</StructureSection>
	[[Category: HIV-1 retropepsin]]		[[Category: HIV-1 retropepsin]]
-	[[Category: Human immunodeficiency virus 1]]
	[[Category: Blum, A]]		[[Category: Blum, A]]
	[[Category: Boettcher, J]]		[[Category: Boettcher, J]]

OCA at 13:11, 25 December 2014

OCA — Thu, 25 Dec 2014 13:11:11 GMT

←Older revision		Revision as of 13:11, 25 December 2014
Line 8:		Line 8:
	<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=2zga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zga OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zga RCSB], [http://www.ebi.ac.uk/pdbsum/2zga 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=2zga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zga OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zga RCSB], [http://www.ebi.ac.uk/pdbsum/2zga PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/POL_HV1BR POL_HV1BR]] 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). 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). 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 (By similarity). 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 (By similarity).
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 32:		Line 34:
	[[Category: HIV-1 retropepsin]]		[[Category: HIV-1 retropepsin]]
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]
-	[[Category: Blum, A.]]	+	[[Category: Blum, A]]
-	[[Category: Boettcher, J.]]	+	[[Category: Boettcher, J]]
-	[[Category: Diederich, W E.]]	+	[[Category: Diederich, W E]]
-	[[Category: Heine, A.]]	+	[[Category: Heine, A]]
-	[[Category: Klebe, G.]]	+	[[Category: Klebe, G]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 05:45, 10 October 2014

OCA — Fri, 10 Oct 2014 05:45:21 GMT

←Older revision		Revision as of 05:45, 10 October 2014
Line 2:		Line 2:
	<StructureSection load='2zga' size='340' side='right' caption='[[2zga]], [[Resolution\|resolution]] 1.65Å' scene=''>		<StructureSection load='2zga' size='340' side='right' caption='[[2zga]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2zga]] is a 1 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=2ZGA OCA]. <br>	+	<table><tr><td colspan='2'>[[2zga]] is a 1 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=2ZGA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZGA FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YDP:(3S,4S),-3,4-BIS-[(4-CARBAMOYL-BENZENSULFONYL)-(3-METHYL-BUT-2-ENYL)-AMINO]-PYRROLIDINE'>YDP</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YDP:(3S,4S),-3,4-BIS-[(4-CARBAMOYL-BENZENSULFONYL)-(3-METHYL-BUT-2-ENYL)-AMINO]-PYRROLIDINE'>YDP</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-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">gag-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/~~Glucokinase Glucokinase~~], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.~~2 2~~.7.1.2] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </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=2zga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zga OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zga RCSB], [http://www.ebi.ac.uk/pdbsum/2zga 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=2zga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zga OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zga RCSB], [http://www.ebi.ac.uk/pdbsum/2zga 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 24:		Line 24:
	Two Solutions for the Same Problem: Multiple Binding Modes of Pyrrolidine-Based HIV-1 Protease Inhibitors.,Blum A, Bottcher J, Dorr S, Heine A, Klebe G, Diederich WE J Mol Biol. 2011 Jul 22;410(4):745-55. PMID:21762812<ref>PMID:21762812</ref>		Two Solutions for the Same Problem: Multiple Binding Modes of Pyrrolidine-Based HIV-1 Protease Inhibitors.,Blum A, Bottcher J, Dorr S, Heine A, Klebe G, Diederich WE J Mol Biol. 2011 Jul 22;410(4):745-55. PMID:21762812<ref>PMID:21762812</ref>

-	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, 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>
	== References ==		== References ==

OCA at 07:38, 14 May 2014

OCA — Wed, 14 May 2014 07:38:51 GMT

←Older revision		Revision as of 07:38, 14 May 2014
Line 1:		Line 1:
-	[[~~Image:~~2zga.~~png~~\|~~left~~\|200px]]	+	==HIV-1 protease in complex with a dimethylallyl decorated pyrrolidine based inhibitor (hexagonal space group)==
		+	<StructureSection load='2zga' size='340' side='right' caption='[[2zga]], [[Resolution\|resolution]] 1.65Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2zga]] is a 1 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=2ZGA OCA]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YDP:(3S,4S),-3,4-BIS-[(4-CARBAMOYL-BENZENSULFONYL)-(3-METHYL-BUT-2-ENYL)-AMINO]-PYRROLIDINE'>YDP</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-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/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </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=2zga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zga OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zga RCSB], [http://www.ebi.ac.uk/pdbsum/2zga 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/zg/2zga_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 ==
		+	Structure-based drug design is an integral part of industrial and academic drug discovery projects. Initial lead structures are, in general, optimized in terms of affinity using iterative cycles comprising synthesis, biological evaluation, computational methods, and structural analysis. X-ray crystallography commonly suggests the existence of a single well-defined state, termed binding mode, which is generally assumed to be consistent in a series of similar ligands and therefore used for the following optimization process. During the further development of symmetrically disubstituted 3,4-amino-pyrrolidines as human immunodeficiency virus type 1 protease inhibitors, we discovered that, by modification of the P1/P1' moieties of our lead structure, the activity of the inhibitors towards the active-site mutation Ile84Val was altered, however, not being explainable with the initial underlying structure-activity relationship. The cocrystallization of the most potent derivative in complex with the human immunodeficiency virus type 1 protease surprisingly led to two different crystal forms (P2(1)2(1)2(1) and P6(1)22). Structural analysis revealed two completely different binding modes; the interaction of the pyrrolidine nitrogen atom with the catalytic aspartates remains as the only similarity. The study presented clearly demonstrates that structural biology has to escort the entire lead optimization process not to fail by an initially observed binding orientation.

-	<!--	+	Two Solutions for the Same Problem: Multiple Binding Modes of Pyrrolidine-Based HIV-1 Protease Inhibitors.,Blum A, Bottcher J, Dorr S, Heine A, Klebe G, Diederich WE J Mol Biol. 2011 Jul 22;410(4):745-55. PMID:21762812<ref>PMID:21762812</ref>
-	~~The line below this paragraph~~, ~~containing "STRUCTURE_2zga"~~, ~~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_2zga\| PDB=2zga \| SCENE= }}~~	+

-	~~===HIV-1 protease in complex with~~ a ~~dimethylallyl decorated pyrrolidine based inhibitor (hexagonal space group)===~~	+	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-		+	== References ==
-	~~<!--~~	+	<references/>
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_21762812}}, adds~~ the ~~Publication Abstract to the page~~	+	__TOC__
-	~~(as it appears on PubMed at http://www~~.~~pubmed~~.~~gov), where 21762812 is the PubMed ID number~~.	+	</StructureSection>
-	-->	+
-	~~{{ABSTRACT_PUBMED_21762812}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[2zga]] is a 1 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=2ZGA OCA].~~	+
-		+
-	==~~Reference~~==	+
-	<~~ref group="xtra">PMID:021762812<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: HIV-1 retropepsin]]		[[Category: HIV-1 retropepsin]]
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]

OCA: Protected "2zga" [edit=sysop:move=sysop]

OCA — Wed, 10 Aug 2011 04:47:08 GMT

Protected "2zga" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:47, 10 August 2011

OCA at 04:47, 10 August 2011

OCA — Wed, 10 Aug 2011 04:47:06 GMT

←Older revision		Revision as of 04:47, 10 August 2011
Line 1:		Line 1:
-	~~{{Seed}}~~	+	[[Image:2zga.png\|left\|200px]]
-	[[Image:2zga.~~jpg~~\|left\|200px]]	+

	<!--		<!--
Line 12:		Line 11:
	===HIV-1 protease in complex with a dimethylallyl decorated pyrrolidine based inhibitor (hexagonal space group)===		===HIV-1 protease in complex with a dimethylallyl decorated pyrrolidine based inhibitor (hexagonal space group)===

		+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21762812}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21762812 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21762812}}

	==About this Structure==		==About this Structure==
-	~~2ZGA~~ is a 1 chain structure of 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=2ZGA OCA].	+	[[2zga]] is a 1 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=2ZGA OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021762812</ref><references group="xtra"/>
	[[Category: HIV-1 retropepsin]]		[[Category: HIV-1 retropepsin]]
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]
Line 22:		Line 30:
	[[Category: Heine, A.]]		[[Category: Heine, A.]]
	[[Category: Klebe, G.]]		[[Category: Klebe, G.]]
-	[[Category: Hydrolase]]	+	[[Category: Hydrolase-hydrolase inhibitor complex]]
-	~~[[Category: Protein~~-~~ligand~~ complex]]	+
-		+
-	~~''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 4 11:22:38 2009''~~	+

OCA at 09:22, 4 February 2009

OCA — Wed, 04 Feb 2009 09:22:46 GMT

←Older revision		Revision as of 09:22, 4 February 2009
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{Seed}}
		+	[[Image:2zga.jpg\|left\|200px]]

-	The ~~entry 2zga~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_2zga", 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_2zga\| PDB=2zga \| SCENE= }}

-	~~Authors: Boettcher, J., Blum, A., Heine, A., Diederich, W.E., Klebe, G.~~	+	===HIV-1 protease in complex with a dimethylallyl decorated pyrrolidine based inhibitor (hexagonal space group)===

-	Description: HIV-1 protease in complex with a dimethylallyl decorated pyrrolidine based inhibitor (hexagonal space group)

		+	==About this Structure==
		+	2ZGA is a 1 chain structure of 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=2ZGA OCA].
		+	[[Category: HIV-1 retropepsin]]
		+	[[Category: Human immunodeficiency virus 1]]
		+	[[Category: Blum, A.]]
		+	[[Category: Boettcher, J.]]
		+	[[Category: Diederich, W E.]]
		+	[[Category: Heine, A.]]
		+	[[Category: Klebe, G.]]
		+	[[Category: Hydrolase]]
		+	[[Category: Protein-ligand complex]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Jun~~ 11 09:08:~~18 2008~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 4 11:22:38 2009''