3r0w

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==Crystal Structures of Multidrug-resistant HIV-1 Protease in Complex with Mechanism-Based Aspartyl Protease Inhibitors.==
==Crystal Structures of Multidrug-resistant HIV-1 Protease in Complex with Mechanism-Based Aspartyl Protease Inhibitors.==
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<StructureSection load='3r0w' size='340' side='right' caption='[[3r0w]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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<StructureSection load='3r0w' size='340' side='right'caption='[[3r0w]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3r0w]] 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=3R0W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R0W FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3r0w]] 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=3R0W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R0W FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RSY:N-[(2R)-1-{[(2S,3S)-5-{[(2R)-1-{[(2S)-1-AMINO-4-METHYL-1-OXOPENTAN-2-YL]AMINO}-3-CHLORO-1-OXOPROPAN-2-YL]AMINO}-3-HYDROXY-5-OXO-1-PHENYLPENTAN-2-YL]AMINO}-3-METHYL-1-OXOBUTAN-2-YL]PYRIDINE-2-CARBOXAMIDE'>RSY</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3r0y|3r0y]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RSY:N-[(2R)-1-{[(2S,3S)-5-{[(2R)-1-{[(2S)-1-AMINO-4-METHYL-1-OXOPENTAN-2-YL]AMINO}-3-CHLORO-1-OXOPROPAN-2-YL]AMINO}-3-HYDROXY-5-OXO-1-PHENYLPENTAN-2-YL]AMINO}-3-METHYL-1-OXOBUTAN-2-YL]PYRIDINE-2-CARBOXAMIDE'>RSY</scene></td></tr>
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<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=3r0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r0w OCA], [http://pdbe.org/3r0w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3r0w RCSB], [http://www.ebi.ac.uk/pdbsum/3r0w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3r0w ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3r0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r0w OCA], [https://pdbe.org/3r0w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r0w RCSB], [https://www.ebi.ac.uk/pdbsum/3r0w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r0w ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/Q000H7_9HIV1 Q000H7_9HIV1]
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Two potent inhibitors (compounds 1 and 2) of malarial aspartyl protease, plasmepsin-II, were evaluated against wild type (NL4-3) and multidrug-resistant clinical isolate 769 (MDR) variants of human immunodeficiency virus type-1 (HIV-1) aspartyl protease. Enzyme inhibition assays showed that both 1 and 2 have better potency against NL4-3 than against MDR protease. Crystal structures of MDR protease in complex with 1 and 2 were solved and analyzed. Crystallographic analysis revealed that the MDR protease exhibits a typical wide-open conformation of the flaps (Gly48 to Gly52) causing an overall expansion in the active site cavity, which, in turn caused unstable binding of the inhibitors. Due to the expansion of the active site cavity, both compounds showed loss of direct contacts with the MDR protease compared to the docking models of NL4-3. Multiple water molecules showed a rich network of hydrogen bonds contributing to the stability of the ligand binding in the distorted binding pockets of the MDR protease in both crystal structures. Docking analysis of 1 and 2 showed a decrease in the binding affinity for both compounds against MDR supporting our structure-function studies. Thus, compounds 1 and 2 show promising inhibitory activity against HIV-1 protease variants and hence are good candidates for further development to enhance their potency against NL4-3 as well as MDR HIV-1 protease variants.
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Crystal structures of multidrug-resistant HIV-1 protease in complex with two potent anti-malarial compounds.,Yedidi RS, Liu Z, Wang Y, Brunzelle JS, Kovari IA, Woster PM, Kovari LC, Gupta D Biochem Biophys Res Commun. 2012 Mar 24. PMID:22469467<ref>PMID:22469467</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3r0w" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
*[[Immunodeficiency virus protease 3D structures|Immunodeficiency virus protease 3D structures]]
*[[Immunodeficiency virus protease 3D structures|Immunodeficiency virus protease 3D structures]]
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== References ==
 
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<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Brunzelle, J]]
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[[Category: Human immunodeficiency virus 1]]
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[[Category: Gupta, D]]
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[[Category: Large Structures]]
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[[Category: Kovari, I A]]
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[[Category: Brunzelle J]]
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[[Category: Kovari, L C]]
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[[Category: Gupta D]]
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[[Category: Liu, Z]]
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[[Category: Kovari IA]]
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[[Category: Woster, P M]]
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[[Category: Kovari LC]]
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[[Category: Yedidi, R S]]
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[[Category: Liu Z]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: Woster PM]]
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[[Category: Yedidi RS]]

Current revision

Crystal Structures of Multidrug-resistant HIV-1 Protease in Complex with Mechanism-Based Aspartyl Protease Inhibitors.

PDB ID 3r0w

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