2whh - Revision history

OCA at 15:56, 13 December 2023

OCA — Wed, 13 Dec 2023 15:56:26 GMT

←Older revision		Revision as of 15:56, 13 December 2023
Line 3:		Line 3:
	<StructureSection load='2whh' size='340' side='right'caption='[[2whh]], [[Resolution\|resolution]] 1.69Å' scene=''>		<StructureSection load='2whh' size='340' side='right'caption='[[2whh]], [[Resolution\|resolution]] 1.69Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2whh]] 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=2WHH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WHH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2whh]] 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=2WHH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WHH FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>~~, ~~<scene name='pdbligand=PPN:PARA-NITROPHENYLALANINE'>PPN</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]] 1.69Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=PPN:PARA-NITROPHENYLALANINE'>PPN</scene></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=2whh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2whh OCA], [https://pdbe.org/2whh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2whh RCSB], [https://www.ebi.ac.uk/pdbsum/2whh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2whh 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=2whh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2whh OCA], [https://pdbe.org/2whh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2whh RCSB], [https://www.ebi.ac.uk/pdbsum/2whh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2whh ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/POL_HV1H2 POL_HV1H2] Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to play a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. It binds in the cytoplasm the human BAF protein which prevent autointegration of the viral genome, and might be included in virions at the ration of zero to 3 BAF dimer per virion. The myristoylation signal and the NLS thus exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles (By similarity).<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 31:		Line 33:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~HIV-~~1 ~~retropepsin~~]]	+	[[Category: Human immunodeficiency virus 1]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bihani, S]]	+	[[Category: Bihani S]]
-	[[Category: Das, A]]	+	[[Category: Das A]]
-	[[Category: Ferrer~~, J L~~]]	+	[[Category: Ferrer JL]]
-	[[Category: Hosur~~, M V~~]]	+	[[Category: Hosur MV]]
-	[[Category: Prashar, V]]	+	[[Category: Prashar V]]
-	~~[[Category: Aspartyl protease]]~~	+
-	~~[[Category: Catalytic mechanism]]~~	+
-	~~[[Category: Drug design]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Multifunctional enzyme]]~~	+
-	~~[[Category: Nucleotidyltransferase]]~~	+
-	~~[[Category: Protease]]~~	+
-	~~[[Category: Rna-directed dna polymerase]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transition state~~]]	+

OCA at 11:07, 6 April 2022

OCA — Wed, 06 Apr 2022 11:07:24 GMT

←Older revision		Revision as of 11:07, 6 April 2022
Line 3:		Line 3:
	<StructureSection load='2whh' size='340' side='right'caption='[[2whh]], [[Resolution\|resolution]] 1.69Å' scene=''>		<StructureSection load='2whh' size='340' side='right'caption='[[2whh]], [[Resolution\|resolution]] 1.69Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2whh]] 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=2WHH OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=2WHH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2whh]] 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=2WHH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WHH FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=PPN:PARA-NITROPHENYLALANINE'>PPN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=PPN:PARA-NITROPHENYLALANINE'>PPN</scene></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~~://proteopedia.org/fgij/fg.htm?mol=2whh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2whh OCA], [~~http~~://pdbe.org/2whh PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2whh RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2whh PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2whh 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=2whh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2whh OCA], [https://pdbe.org/2whh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2whh RCSB], [https://www.ebi.ac.uk/pdbsum/2whh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2whh ProSAT]</span></td></tr>
	</table>		</table>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==

OCA at 08:44, 1 July 2020

OCA — Wed, 01 Jul 2020 08:44:20 GMT

←Older revision		Revision as of 08:44, 1 July 2020
Line 1:		Line 1:

	==HIV-1 protease tethered dimer Q-product complex along with nucleophilic water molecule==		==HIV-1 protease tethered dimer Q-product complex along with nucleophilic water molecule==
-	<StructureSection load='2whh' size='340' side='right' caption='[[2whh]], [[Resolution\|resolution]] 1.69Å' scene=''>	+	<StructureSection load='2whh' size='340' side='right'caption='[[2whh]], [[Resolution\|resolution]] 1.69Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2whh]] 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=2WHH OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2WHH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2whh]] 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=2WHH OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2WHH FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=PPN:PARA-NITROPHENYLALANINE'>PPN</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=PPN:PARA-NITROPHENYLALANINE'>PPN</scene></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=2whh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2whh OCA], [http://pdbe.org/2whh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2whh RCSB], [http://www.ebi.ac.uk/pdbsum/2whh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2whh ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2whh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2whh OCA], [http://pdbe.org/2whh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2whh RCSB], [http://www.ebi.ac.uk/pdbsum/2whh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2whh ProSAT]</span></td></tr>
	</table>		</table>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
Line 32:		Line 32:
	</StructureSection>		</StructureSection>
	[[Category: HIV-1 retropepsin]]		[[Category: HIV-1 retropepsin]]
		+	[[Category: Large Structures]]
	[[Category: Bihani, S]]		[[Category: Bihani, S]]
	[[Category: Das, A]]		[[Category: Das, A]]

OCA at 09:25, 26 September 2018

OCA — Wed, 26 Sep 2018 09:25:56 GMT

←Older revision		Revision as of 09:25, 26 September 2018
Line 1:		Line 1:

-	==HIV-1 ~~PROTEASE TETHERED DIMER~~ Q-~~PRODUCT COMPLEX ALONG WITH NUCLEOPHILIC WATER MOLECULE~~==	+	==HIV-1 protease tethered dimer Q-product complex along with nucleophilic water molecule==
	<StructureSection load='2whh' size='340' side='right' caption='[[2whh]], [[Resolution\|resolution]] 1.69Å' scene=''>		<StructureSection load='2whh' size='340' side='right' caption='[[2whh]], [[Resolution\|resolution]] 1.69Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
Line 12:		Line 12:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wh/2whh_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wh/2whh_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>

OCA at 20:06, 11 August 2016

OCA — Thu, 11 Aug 2016 20:06:07 GMT

←Older revision		Revision as of 20:06, 11 August 2016
Line 1:		Line 1:
		+
	==HIV-1 PROTEASE TETHERED DIMER Q-PRODUCT COMPLEX ALONG WITH NUCLEOPHILIC WATER MOLECULE==		==HIV-1 PROTEASE TETHERED DIMER Q-PRODUCT COMPLEX ALONG WITH NUCLEOPHILIC WATER MOLECULE==
	<StructureSection load='2whh' size='340' side='right' caption='[[2whh]], [[Resolution\|resolution]] 1.69Å' scene=''>		<StructureSection load='2whh' size='340' side='right' caption='[[2whh]], [[Resolution\|resolution]] 1.69Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2whh]] 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=2WHH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WHH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2whh]] 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=2WHH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WHH FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=PPN:PARA-NITROPHENYLALANINE'>PPN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=PPN:PARA-NITROPHENYLALANINE'>PPN</scene></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=2whh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2whh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2whh RCSB], [http://www.ebi.ac.uk/pdbsum/2whh 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=2whh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2whh OCA], [http://pdbe.org/2whh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2whh RCSB], [http://www.ebi.ac.uk/pdbsum/2whh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2whh ProSAT]</span></td></tr>
	</table>		</table>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
Line 15:		Line 16:
	<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=2whh ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 25:		Line 26:
	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 2whh" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
Line 30:		Line 32:
	</StructureSection>		</StructureSection>
	[[Category: HIV-1 retropepsin]]		[[Category: HIV-1 retropepsin]]
-	[[Category: Human immunodeficiency virus 1]]
	[[Category: Bihani, S]]		[[Category: Bihani, S]]
	[[Category: Das, A]]		[[Category: Das, A]]

OCA at 10:34, 20 January 2015

OCA — Tue, 20 Jan 2015 10:34:55 GMT

←Older revision		Revision as of 10:34, 20 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2whh]] 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=2WHH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WHH FirstGlance]. <br>		<table><tr><td colspan='2'>[[2whh]] 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=2WHH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WHH FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=PPN:PARA-NITROPHENYLALANINE'>PPN</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=PPN:PARA-NITROPHENYLALANINE'>PPN</scene></td></tr>
-	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2whh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2whh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2whh RCSB], [http://www.ebi.ac.uk/pdbsum/2whh 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=2whh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2whh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2whh RCSB], [http://www.ebi.ac.uk/pdbsum/2whh 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 31:		Line 31:
	[[Category: HIV-1 retropepsin]]		[[Category: HIV-1 retropepsin]]
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]
-	[[Category: Bihani, S.]]	+	[[Category: Bihani, S]]
-	[[Category: Das, A.]]	+	[[Category: Das, A]]
-	[[Category: Ferrer, J L.]]	+	[[Category: Ferrer, J L]]
-	[[Category: Hosur, M V.]]	+	[[Category: Hosur, M V]]
-	[[Category: Prashar, V.]]	+	[[Category: Prashar, V]]
	[[Category: Aspartyl protease]]		[[Category: Aspartyl protease]]
	[[Category: Catalytic mechanism]]		[[Category: Catalytic mechanism]]

OCA at 01:34, 1 October 2014

OCA — Wed, 01 Oct 2014 01:34:07 GMT

←Older revision		Revision as of 01:34, 1 October 2014
Line 1:		Line 1:
-	[[~~Image~~:2whh.~~png\|left~~\|200px]]	+	==HIV-1 PROTEASE TETHERED DIMER Q-PRODUCT COMPLEX ALONG WITH NUCLEOPHILIC WATER MOLECULE==
		+	<StructureSection load='2whh' size='340' side='right' caption='[[2whh]], [[Resolution\|resolution]] 1.69Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2whh]] 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=2WHH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WHH FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=PPN:PARA-NITROPHENYLALANINE'>PPN</scene><br>
		+	<tr><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=2whh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2whh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2whh RCSB], [http://www.ebi.ac.uk/pdbsum/2whh 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/wh/2whh_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 ==
		+	BACKGROUND: It is known that HIV-1 protease is an important target for design of antiviral compounds in the treatment of Acquired Immuno Deficiency Syndrome (AIDS). In this context, understanding the catalytic mechanism of the enzyme is of crucial importance as transition state structure directs inhibitor design. Most mechanistic proposals invoke nucleophilic attack on the scissile peptide bond by a water molecule. But such a water molecule coexisting with any ligand in the active site has not been found so far in the crystal structures. PRINCIPAL FINDINGS: We report here the first observation of the coexistence in the active site, of a water molecule WAT1, along with the carboxyl terminal product (Q product) peptide. The product peptide has been generated in situ through cleavage of the full-length substrate. The N-terminal product (P product) has diffused out and is replaced by a set of water molecules while the Q product is still held in the active site through hydrogen bonds. The position of WAT1, which hydrogen bonds to both the catalytic aspartates, is different from when there is no substrate bound in the active site. We propose WAT1 to be the position from where catalytic water attacks the scissile peptide bond. Comparison of structures of HIV-1 protease complexed with the same oligopeptide substrate, but at pH 2.0 and at pH 7.0 shows interesting changes in the conformation and hydrogen bonding interactions from the catalytic aspartates. CONCLUSIONS/SIGNIFICANCE: The structure is suggestive of the repositioning, during substrate binding, of the catalytic water for activation and subsequent nucleophilic attack. The structure could be a snap shot of the enzyme active site primed for the next round of catalysis. This structure further suggests that to achieve the goal of designing inhibitors mimicking the transition-state, the hydrogen-bonding pattern between WAT1 and the enzyme should be replicated.

-	~~{{STRUCTURE_2whh\| PDB=2whh \| SCENE= }}~~	+	Catalytic water co-existing with a product peptide in the active site of HIV-1 protease revealed by X-ray structure analysis.,Prashar V, Bihani S, Das A, Ferrer JL, Hosur M PLoS One. 2009 Nov 17;4(11):e7860. PMID:19924250<ref>PMID:19924250</ref>

-	~~===HIV-1 PROTEASE TETHERED DIMER Q-PRODUCT COMPLEX ALONG WITH NUCLEOPHILIC WATER MOLECULE===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_19924250}}~~	+	== References ==
-		+	<references/>
-	~~==About this Structure==~~	+	__TOC__
-	~~[[2whh]] 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=2WHH OCA].~~	+	</StructureSection>
-		+
-	==~~Reference~~==	+
-	<~~ref group="xtra">PMID:019924250<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: HIV-1 retropepsin]]		[[Category: HIV-1 retropepsin]]
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]

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

OCA — Mon, 07 Jan 2013 22:23:46 GMT

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

←Older revision

Revision as of 22:23, 7 January 2013

OCA at 22:23, 7 January 2013

OCA — Mon, 07 Jan 2013 22:23:37 GMT

←Older revision		Revision as of 22:23, 7 January 2013
Line 1:		Line 1:
-	{{Seed}}
	[[Image:2whh.png\|left\|200px]]		[[Image:2whh.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_2whh", 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_2whh\| PDB=2whh \| SCENE= }}		{{STRUCTURE_2whh\| PDB=2whh \| SCENE= }}

	===HIV-1 PROTEASE TETHERED DIMER Q-PRODUCT COMPLEX ALONG WITH NUCLEOPHILIC WATER MOLECULE===		===HIV-1 PROTEASE TETHERED DIMER Q-PRODUCT COMPLEX ALONG WITH NUCLEOPHILIC WATER MOLECULE===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_19924250}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 19924250 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_19924250}}		{{ABSTRACT_PUBMED_19924250}}

	==About this Structure==		==About this Structure==
-	~~2WHH~~ 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=2WHH OCA].	+	[[2whh]] 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=2WHH OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~19924250~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019924250</ref><references group="xtra"/>
	[[Category: HIV-1 retropepsin]]		[[Category: HIV-1 retropepsin]]
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]
Line 41:		Line 29:
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Transition state]]		[[Category: Transition state]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 23 08:38:44 2010''

OCA at 04:33, 23 June 2010

OCA — Wed, 23 Jun 2010 04:33:26 GMT

←Older revision		Revision as of 04:33, 23 June 2010
Line 1:		Line 1:
	{{Seed}}		{{Seed}}
-	[[Image:2whh.~~jpg~~\|left\|200px]]	+	[[Image:2whh.png\|left\|200px]]

	<!--		<!--
Line 20:		Line 20:

	==About this Structure==		==About this Structure==
-	2WHH 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=2WHH OCA].	+	2WHH 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=2WHH OCA].

	==Reference==		==Reference==
Line 34:		Line 34:
	[[Category: Catalytic mechanism]]		[[Category: Catalytic mechanism]]
	[[Category: Drug design]]		[[Category: Drug design]]
-	[[Category: Hiv-1 protease]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Multifunctional enzyme]]		[[Category: Multifunctional enzyme]]
Line 43:		Line 42:
	[[Category: Transition state]]		[[Category: Transition state]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Dec 2 10~~:01:~~52 2009~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 23 08:38:44 2010''