4hvp - Revision history

OCA at 04:58, 13 February 2020

OCA — Thu, 13 Feb 2020 04:58:05 GMT

←Older revision		Revision as of 04:58, 13 February 2020
Line 1:		Line 1:

	==Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 Angstroms resolution==		==Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 Angstroms resolution==
-	<StructureSection load='4hvp' size='340' side='right' caption='[[4hvp]], [[Resolution\|resolution]] 2.30Å' scene=''>	+	<StructureSection load='4hvp' size='340' side='right'caption='[[4hvp]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4hvp]] 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=4HVP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HVP FirstGlance]. <br>		<table><tr><td colspan='2'>[[4hvp]] 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=4HVP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HVP FirstGlance]. <br>
Line 14:		Line 14:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hv/4hvp_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hv/4hvp_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 29:		Line 29:
	</div>		</div>
	<div class="pdbe-citations 4hvp" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4hvp" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Immunodeficiency virus protease 3D structures\|Immunodeficiency virus protease 3D structures]]
		+	*[[Journal:Acta Cryst D:S2059798319011355\|Journal:Acta Cryst D:S2059798319011355]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Clawson, L]]		[[Category: Clawson, L]]
	[[Category: Kent, S B.H]]		[[Category: Kent, S B.H]]

OCA at 07:20, 29 November 2017

OCA — Wed, 29 Nov 2017 07:20:11 GMT

←Older revision		Revision as of 07:20, 29 November 2017
Line 1:		Line 1:
		+
	==Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 Angstroms resolution==		==Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 Angstroms resolution==
	<StructureSection load='4hvp' size='340' side='right' caption='[[4hvp]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4hvp' size='340' side='right' caption='[[4hvp]], [[Resolution\|resolution]] 2.30Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2NC:N-{(2S)-2-[(N-ACETYL-L-THREONYL-L-ISOLEUCYL)AMINO]HEXYL}-L-NORLEUCYL-L-GLUTAMINYL-N~5~-[AMINO(IMINIO)METHYL]-L-ORNITHINAMIDE'>2NC</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2NC:N-{(2S)-2-[(N-ACETYL-L-THREONYL-L-ISOLEUCYL)AMINO]HEXYL}-L-NORLEUCYL-L-GLUTAMINYL-N~5~-[AMINO(IMINIO)METHYL]-L-ORNITHINAMIDE'>2NC</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene></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=4hvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvp OCA], [http://pdbe.org/4hvp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hvp RCSB], [http://www.ebi.ac.uk/pdbsum/4hvp 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=4hvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvp OCA], [http://pdbe.org/4hvp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hvp RCSB], [http://www.ebi.ac.uk/pdbsum/4hvp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hvp ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 05:25, 8 February 2016

OCA — Mon, 08 Feb 2016 05:25:45 GMT

←Older revision		Revision as of 05:25, 8 February 2016
Line 2:		Line 2:
	<StructureSection load='4hvp' size='340' side='right' caption='[[4hvp]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4hvp' size='340' side='right' caption='[[4hvp]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4hvp]] 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=4HVP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HVP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4hvp]] 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=4HVP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HVP FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2NC:N-{(2S)-2-[(N-ACETYL-L-THREONYL-L-ISOLEUCYL)AMINO]HEXYL}-L-NORLEUCYL-L-GLUTAMINYL-N~5~-[AMINO(IMINIO)METHYL]-L-ORNITHINAMIDE'>2NC</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2NC:N-{(2S)-2-[(N-ACETYL-L-THREONYL-L-ISOLEUCYL)AMINO]HEXYL}-L-NORLEUCYL-L-GLUTAMINYL-N~5~-[AMINO(IMINIO)METHYL]-L-ORNITHINAMIDE'>2NC</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene></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=4hvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hvp RCSB], [http://www.ebi.ac.uk/pdbsum/4hvp 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=4hvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvp OCA], [http://pdbe.org/4hvp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hvp RCSB], [http://www.ebi.ac.uk/pdbsum/4hvp PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 17:
	<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=4hvp ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 27:		Line 27:
	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 4hvp" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Human immunodeficiency virus 1]]
	[[Category: Clawson, L]]		[[Category: Clawson, L]]
	[[Category: Kent, S B.H]]		[[Category: Kent, S B.H]]

OCA at 20:56, 24 December 2014

OCA — Wed, 24 Dec 2014 20:56:56 GMT

←Older revision		Revision as of 20:56, 24 December 2014
Line 7:		Line 7:
	<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=4hvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hvp RCSB], [http://www.ebi.ac.uk/pdbsum/4hvp 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=4hvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hvp RCSB], [http://www.ebi.ac.uk/pdbsum/4hvp PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/POL_HV1A2 POL_HV1A2]] 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]]

OCA at 12:06, 21 December 2014

OCA — Sun, 21 Dec 2014 12:06:37 GMT

←Older revision		Revision as of 12:06, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4hvp\| PDB=4hvp \| SCENE= }}~~	+	==Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 Angstroms resolution==
-	===Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 Angstroms resolution===	+	<StructureSection load='4hvp' size='340' side='right' caption='[[4hvp]], [[Resolution\|resolution]] 2.30Å' scene=''>
-	{~~{ABSTRACT_PUBMED_2686029}~~}	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4hvp]] 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=4HVP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HVP FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2NC:N-{(2S)-2-[(N-ACETYL-L-THREONYL-L-ISOLEUCYL)AMINO]HEXYL}-L-NORLEUCYL-L-GLUTAMINYL-N~5~-[AMINO(IMINIO)METHYL]-L-ORNITHINAMIDE'>2NC</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene></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=4hvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hvp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hvp RCSB], [http://www.ebi.ac.uk/pdbsum/4hvp 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/hv/4hvp_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 structure of a complex between a peptide inhibitor with the sequence N-acetyl-Thr-Ile-Nle-psi[CH2-NH]-Nle-Gln-Arg.amide (Nle, norleucine) with chemically synthesized HIV-1 (human immunodeficiency virus 1) protease was determined at 2.3 A resolution (R factor of 0.176). Despite the symmetric nature of the unliganded enzyme, the asymmetric inhibitor lies in a single orientation and makes extensive interactions at the interface between the two subunits of the homodimeric protein. Compared with the unliganded enzyme, the protein molecule underwent substantial changes, particularly in an extended region corresponding to the "flaps" (residues 35 to 57 in each chain), where backbone movements as large as 7 A are observed.

-	~~==Function==~~	+	Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 A resolution.,Miller M, Schneider J, Sathyanarayana BK, Toth MV, Marshall GR, Clawson L, Selk L, Kent SB, Wlodawer A Science. 1989 Dec 1;246(4934):1149-52. PMID:2686029<ref>PMID:2686029</ref>
-	[[http://www.uniprot.org/uniprot/POL_HV1A2 POL_HV1A2]] 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~~).	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4hvp]] 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=4HVP OCA].~~	+	</div>
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:002686029</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]
-	[[Category: Clawson, L.]]	+	[[Category: Clawson, L]]
-	[[Category: Kent, S B.H.]]	+	[[Category: Kent, S B.H]]
-	[[Category: Marshall, G R.]]	+	[[Category: Marshall, G R]]
-	[[Category: Miller, M.]]	+	[[Category: Miller, M]]
-	[[Category: Sathyanarayana, B K.]]	+	[[Category: Sathyanarayana, B K]]
-	[[Category: Schneider, J.]]	+	[[Category: Schneider, J]]
-	[[Category: Selk, L.]]	+	[[Category: Selk, L]]
-	[[Category: Toth, M V.]]	+	[[Category: Toth, M V]]
-	[[Category: Wlodawer, A.]]	+	[[Category: Wlodawer, A]]
	[[Category: Acid proteinase]]		[[Category: Acid proteinase]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 22:48, 3 April 2013

OCA — Wed, 03 Apr 2013 22:48:46 GMT

←Older revision		Revision as of 22:48, 3 April 2013
Line 1:		Line 1:
-	[[Image:4hvp.png\|left\|200px]]
-
	{{STRUCTURE_4hvp\| PDB=4hvp \| SCENE= }}		{{STRUCTURE_4hvp\| PDB=4hvp \| SCENE= }}
		+	===Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 Angstroms resolution===
		+	{{ABSTRACT_PUBMED_2686029}}

-	===~~Structure~~ of complex of ~~synthetic~~ HIV-1 protease with a ~~stubtrate~~-~~based inhibitor~~ at 2.3 ~~Angstroms resolution===~~	+	==Function==
-		+	[[http://www.uniprot.org/uniprot/POL_HV1A2 POL_HV1A2]] 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).
-	~~{{ABSTRACT_PUBMED_2686029}}~~	+

	==About this Structure==		==About this Structure==
Line 11:		Line 10:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:002686029</ref><references group="xtra"/>	+	<ref group="xtra">PMID:002686029</ref><references group="xtra"/><references/>
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]
	[[Category: Clawson, L.]]		[[Category: Clawson, L.]]

OCA: Protected "4hvp" [edit=sysop:move=sysop]

OCA — Wed, 27 Feb 2013 12:58:12 GMT

Protected "4hvp" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:58, 27 February 2013

OCA at 12:58, 27 February 2013

OCA — Wed, 27 Feb 2013 12:58:11 GMT

←Older revision		Revision as of 12:58, 27 February 2013
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-	{{Seed}}
	[[Image:4hvp.png\|left\|200px]]		[[Image:4hvp.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_4hvp", 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_4hvp\| PDB=4hvp \| SCENE= }}		{{STRUCTURE_4hvp\| PDB=4hvp \| SCENE= }}

-	===~~STRUCTURE OF COMPLEX OF SYNTHETIC~~ HIV-1 ~~PROTEASE WITH A STUBTRATE~~-~~BASED INHIBITOR AT~~ 2.3 ~~ANGSTROMS RESOLUTION~~===	+	===Structure of complex of synthetic HIV-1 protease with a stubtrate-based inhibitor at 2.3 Angstroms resolution===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_2686029}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 2686029 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_2686029}}		{{ABSTRACT_PUBMED_2686029}}

	==About this Structure==		==About this Structure==
-	~~4HVP~~ is a ~~3 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=4HVP OCA].	+	[[4hvp]] 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=4HVP OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~2686029~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:002686029</ref><references group="xtra"/>
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]
	[[Category: Clawson, L.]]		[[Category: Clawson, L.]]
Line 34:		Line 22:
	[[Category: Toth, M V.]]		[[Category: Toth, M V.]]
	[[Category: Wlodawer, A.]]		[[Category: Wlodawer, A.]]
-		+	[[Category: Acid proteinase]]
-	~~''Page seeded by~~ [~~http~~:~~//oca.weizmann.ac.il/oca OCA~~ ] ~~on Mon Feb 16 19~~:~~08:37 2009''~~	+	[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 17:08, 16 February 2009

OCA — Mon, 16 Feb 2009 17:08:38 GMT

←Older revision		Revision as of 17:08, 16 February 2009
Line 20:		Line 20:

	==About this Structure==		==About this Structure==
-	4HVP is a ~~[[Single protein]]~~ 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=4HVP OCA].	+	4HVP is a 3 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=4HVP OCA].

	==Reference==		==Reference==
-	Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 A resolution., Miller M, Schneider J, Sathyanarayana BK, Toth MV, Marshall GR, Clawson L, Selk L, Kent SB, Wlodawer A, Science. 1989 Dec 1;246(4934):1149-52. PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/2686029 2686029]~~	+	<ref group="xtra">PMID:2686029</ref><references group="xtra"/>
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]
-	[[Category: Single protein]]
	[[Category: Clawson, L.]]		[[Category: Clawson, L.]]
	[[Category: Kent, S B.H.]]		[[Category: Kent, S B.H.]]
Line 36:		Line 35:
	[[Category: Wlodawer, A.]]		[[Category: Wlodawer, A.]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Thu Jul 3 13~~:41:~~21 2008~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 19:08:37 2009''

OCA at 10:41, 3 July 2008

OCA — Thu, 03 Jul 2008 10:41:21 GMT

←Older revision		Revision as of 10:41, 3 July 2008
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-	[[Image:4hvp.~~gif~~\|left\|200px]]	+	{{Seed}}
		+	[[Image:4hvp.png\|left\|200px]]

	<!--		<!--
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	{{STRUCTURE_4hvp\| PDB=4hvp \| SCENE= }}		{{STRUCTURE_4hvp\| PDB=4hvp \| SCENE= }}

-	~~'''~~STRUCTURE OF COMPLEX OF SYNTHETIC HIV-1 PROTEASE WITH A STUBTRATE-BASED INHIBITOR AT 2.3 ANGSTROMS RESOLUTION~~'''~~	+	===STRUCTURE OF COMPLEX OF SYNTHETIC HIV-1 PROTEASE WITH A STUBTRATE-BASED INHIBITOR AT 2.3 ANGSTROMS RESOLUTION===


-	~~==Overview==~~	+	<!--
-	The ~~structure of a complex between a peptide inhibitor with the sequence N-acetyl-Thr-Ile-Nle-psi[CH2-NH]-Nle-Gln-Arg.amide (Nle~~, ~~norleucine) with chemically synthesized HIV-1 (human immunodeficiency virus 1) protease was determined at 2.3 A resolution (R factor of 0.176). Despite the symmetric nature of the unliganded enzyme~~, the asymmetric inhibitor lies in a single orientation and makes extensive interactions at the interface between the two subunits of the homodimeric protein. Compared with the unliganded enzyme, the protein molecule underwent substantial changes, particularly in an extended region corresponding to the ~~"flaps"~~ (~~residues 35 to 57 in each chain~~), where ~~backbone movements as large as 7 A are observed~~.	+	The line below this paragraph, {{ABSTRACT_PUBMED_2686029}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 2686029 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_2686029}}

	==About this Structure==		==About this Structure==
Line 31:		Line 35:
	[[Category: Toth, M V.]]		[[Category: Toth, M V.]]
	[[Category: Wlodawer, A.]]		[[Category: Wlodawer, A.]]
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sun May~~ ~~4 22~~:25:24 2008''	+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jul 3 13:41:21 2008''