5uov: Difference between revisions
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==HIV-1 wild Type protease with GRL-1118A , an isophthalamide-derived P2-P3 ligand with the sulfonamide isostere as the P2' group== | |||
<StructureSection load='5uov' size='340' side='right' caption='[[5uov]], [[Resolution|resolution]] 1.33Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5uov]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UOV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UOV FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8FP:N-[(2S,3R)-3-HYDROXY-4-{[(4-METHOXYPHENYL)SULFONYL](2-METHYLPROPYL)AMINO}-1-PHENYLBUTAN-2-YL]-3-[(2R)-2-(4-METHYL-1,3-THIAZOL-2-YL)PYRROLIDINE-1-CARBONYL]BENZAMIDE'>8FP</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ult|5ult]], [[5upz|5upz]]</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=5uov FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uov OCA], [http://pdbe.org/5uov PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uov RCSB], [http://www.ebi.ac.uk/pdbsum/5uov PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uov ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Based upon molecular insights from the X-ray structures of inhibitor-bound HIV-1 protease complexes, we have designed a series of isophthalamide-derived inhibitors incorporating substituted pyrrolidines, piperidines and thiazolidines as P2-P3 ligands for specific interactions in the S2-S3 extended site. Compound 4b has shown an enzyme Ki of 0.025nM and antiviral IC50 of 69nM. An X-ray crystal structure of inhibitor 4b-HIV-1 protease complex was determined at 1.33A resolution. We have also determined X-ray structure of 3b-bound HIV-1 protease at 1.27A resolution. These structures revealed important molecular insight into the inhibitor-HIV-1 protease interactions in the active site. | |||
Design of novel HIV-1 protease inhibitors incorporating isophthalamide-derived P2-P3 ligands: Synthesis, biological evaluation and X-ray structural studies of inhibitor-HIV-1 protease complex.,Ghosh AK, Brindisi M, Nyalapatla PR, Takayama J, Ella-Menye JR, Yashchuk S, Agniswamy J, Wang YF, Aoki M, Amano M, Weber IT, Mitsuya H Bioorg Med Chem. 2017 Apr 9. pii: S0968-0896(17)30731-9. doi:, 10.1016/j.bmc.2017.04.005. PMID:28434781<ref>PMID:28434781</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5uov" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Agniswamy, J]] | [[Category: Agniswamy, J]] | ||
[[Category: Wang, Y F]] | |||
[[Category: Weber, I T]] | |||
[[Category: An isophthalamide-derived p2-p3 ligand]] | |||
[[Category: Darunavir]] | |||
[[Category: Hiv-1 protease inhibitor grl-1118a]] | |||
[[Category: Hydrolase inhibitor complex]] | |||
[[Category: Hydrolase-hydrolase inhibitor complex]] | |||
[[Category: Multidrug-resistant]] | |||
