5t2z - Revision history

OCA at 12:53, 4 October 2023

OCA — Wed, 04 Oct 2023 12:53:44 GMT

←Older revision		Revision as of 12:53, 4 October 2023
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	<StructureSection load='5t2z' size='340' side='right'caption='[[5t2z]], [[Resolution\|resolution]] 1.50Å' scene=''>		<StructureSection load='5t2z' size='340' side='right'caption='[[5t2z]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5t2z]] 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=5T2Z OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5T2Z FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5t2z]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T2Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5T2Z FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=017:(3R,3AS,6AR)-HEXAHYDROFURO[2,3-B]FURAN-3-YL(1S,2R)-3-[[(4-AMINOPHENYL)SULFONYL](ISOBUTYL)AMINO]-1-BENZYL-2-HYDROXYPROPYLCARBAMATE'>017</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]] 1.5Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5t2e\|5t2e]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=017:(3R,3AS,6AR)-HEXAHYDROFURO[2,3-B]FURAN-3-YL(1S,2R)-3-[[(4-AMINOPHENYL)SULFONYL](ISOBUTYL)AMINO]-1-BENZYL-2-HYDROXYPROPYLCARBAMATE'>017</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])~~</td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5t2z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t2z OCA], [https://pdbe.org/5t2z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5t2z RCSB], [https://www.ebi.ac.uk/pdbsum/5t2z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5t2z ProSAT]</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=5t2z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t2z OCA], [~~http~~://pdbe.org/5t2z PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5t2z RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5t2z PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5t2z ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/I7BFC3_9HIV1 I7BFC3_9HIV1]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human immunodeficiency virus 1]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Agniswamy, J]]	+	[[Category: Agniswamy J]]
-	[[Category: Weber~~, I T]]~~	+	[[Category: Weber IT]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Protease~~]]	+

OCA at 09:22, 4 December 2019

OCA — Wed, 04 Dec 2019 09:22:05 GMT

←Older revision		Revision as of 09:22, 4 December 2019
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	==Crystal Structure of Multi-drug Resistant HIV-1 Protease PR-S17 in Complex with Darunavir==		==Crystal Structure of Multi-drug Resistant HIV-1 Protease PR-S17 in Complex with Darunavir==
-	<StructureSection load='5t2z' size='340' side='right' caption='[[5t2z]], [[Resolution\|resolution]] 1.50Å' scene=''>	+	<StructureSection load='5t2z' size='340' side='right'caption='[[5t2z]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5t2z]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T2Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T2Z FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5t2z]] 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=5T2Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T2Z FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=017:(3R,3AS,6AR)-HEXAHYDROFURO[2,3-B]FURAN-3-YL(1S,2R)-3-[[(4-AMINOPHENYL)SULFONYL](ISOBUTYL)AMINO]-1-BENZYL-2-HYDROXYPROPYLCARBAMATE'>017</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=017:(3R,3AS,6AR)-HEXAHYDROFURO[2,3-B]FURAN-3-YL(1S,2R)-3-[[(4-AMINOPHENYL)SULFONYL](ISOBUTYL)AMINO]-1-BENZYL-2-HYDROXYPROPYLCARBAMATE'>017</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5t2e\|5t2e]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5t2e\|5t2e]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5t2z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t2z OCA], [http://pdbe.org/5t2z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t2z RCSB], [http://www.ebi.ac.uk/pdbsum/5t2z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t2z ProSAT]</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=5t2z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t2z OCA], [http://pdbe.org/5t2z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t2z RCSB], [http://www.ebi.ac.uk/pdbsum/5t2z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t2z ProSAT]</span></td></tr>
	</table>		</table>
Line 17:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 5t2z" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5t2z" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Immunodeficiency virus protease 3D structures\|Immunodeficiency virus protease 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Agniswamy, J]]		[[Category: Agniswamy, J]]
	[[Category: Weber, I T]]		[[Category: Weber, I T]]

OCA at 16:37, 18 January 2017

OCA — Wed, 18 Jan 2017 16:37:28 GMT

←Older revision		Revision as of 16:37, 18 January 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5t2z is ~~ON HOLD until Paper~~ Publication	+	==Crystal Structure of Multi-drug Resistant HIV-1 Protease PR-S17 in Complex with Darunavir==
		+	<StructureSection load='5t2z' size='340' side='right' caption='[[5t2z]], [[Resolution\|resolution]] 1.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5t2z]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T2Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T2Z FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=017:(3R,3AS,6AR)-HEXAHYDROFURO[2,3-B]FURAN-3-YL(1S,2R)-3-[[(4-AMINOPHENYL)SULFONYL](ISOBUTYL)AMINO]-1-BENZYL-2-HYDROXYPROPYLCARBAMATE'>017</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5t2e\|5t2e]]</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=5t2z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t2z OCA], [http://pdbe.org/5t2z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t2z RCSB], [http://www.ebi.ac.uk/pdbsum/5t2z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t2z ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	We report structural analysis of HIV protease variant PRS17 which was rationally selected by machine learning to represent wide classes of highly drug-resistant variants. Crystal structures were solved of PRS17 in the inhibitor-free form and in complex with antiviral inhibitor, darunavir. Despite its 17 mutations, PRS17 has only one mutation (V82S) in the inhibitor/substrate binding cavity, yet exhibits high resistance to all clinical inhibitors. PRS17 has none of the major mutations (I47V, I50V, I54ML, L76V and I84V) associated with darunavir resistance, but has 10,000-fold weaker binding affinity relative to the wild type PR. Comparable binding affinity of 8000-fold weaker than PR is seen for drug resistant mutant PR20, which bears 3 mutations associated with major resistance to darunavir (I47V, I54L and I84V). Inhibitor-free PRS17 shows an open flap conformation with a curled tip correlating with G48V flap mutation. NMR studies on inactive PRS17 D25N unambiguously confirm that the flaps adopt mainly an open conformation in solution very similar to that in the inhibitor-free crystal structure. In PRS17, the hinge loop cluster of mutations, E35D, M36I and S37D, contributes to the altered flap dynamics by a mechanism similar to that of PR20. An additional K20R mutation anchors an altered conformation of the hinge loop. Flap mutations M46L and G48V in PRS17/DRV complex alter the Phe53 conformation by steric hindrance between the side chains. Unlike the L10F mutation in PR20, L10I in PRS17 does not break the inter-subunit ion pair or diminish the dimer stability, consistent with a very low dimer dissociation constant comparable to that of wild type PR. Distal mutations A71V, L90M and I93L propagate alterations to the catalytic site of PRS17. PRS17 exhibits a molecular mechanism whereby mutations act synergistically to alter the flap dynamics resulting in significantly weaker binding yet maintaining active site contacts with darunavir.

-	~~Authors:~~ Agniswamy, J., ~~Weber~~, I.T.	+	Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics.,Agniswamy J, Louis JM, Roche J, Harrison RW, Weber IT PLoS One. 2016 Dec 16;11(12):e0168616. doi: 10.1371/journal.pone.0168616., eCollection 2016. PMID:27992544<ref>PMID:27992544</ref>

-	~~Description: Crystal Structure~~ of ~~Multi~~-~~drug Resistant HIV~~-~~1 Protease PR-S17 in Complex with Darunavir~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	~~[[Category: Weber, I.T]]~~	+	<div class="pdbe-citations 5t2z" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Agniswamy, J]]		[[Category: Agniswamy, J]]
		+	[[Category: Weber, I T]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Inhibitor]]
		+	[[Category: Protease]]

OCA: Protected "5t2z" [edit=sysop:move=sysop]

OCA — Fri, 09 Sep 2016 15:37:33 GMT

Protected "5t2z" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:37, 9 September 2016

OCA: New page: '''Unreleased structure''' The entry 5t2z is ON HOLD until Paper Publication Authors: Agniswamy, J., Weber, I.T. Description: Crystal Structure of Multi-drug Resistant HIV-1 Protease P...

OCA — Fri, 09 Sep 2016 15:37:32 GMT

New page: '''Unreleased structure''' The entry 5t2z is ON HOLD until Paper Publication Authors: Agniswamy, J., Weber, I.T. Description: Crystal Structure of Multi-drug Resistant HIV-1 Protease P...

New page

'''Unreleased structure'''

The entry 5t2z is ON HOLD until Paper Publication

Authors: Agniswamy, J., Weber, I.T.

Description: Crystal Structure of Multi-drug Resistant HIV-1 Protease PR-S17 in Complex with Darunavir
[[Category: Unreleased Structures]]
[[Category: Weber, I.T]]
[[Category: Agniswamy, J]]