6c8x
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Wild-type HIV-1 protease in complex with a phenylboronic acid (P2') analog of darunavir== | |
| + | <StructureSection load='6c8x' size='340' side='right' caption='[[6c8x]], [[Resolution|resolution]] 1.61Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6c8x]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C8X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6C8X FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BVR:[4-[[(2~{R},3~{S})-3-[[(3~{a}~{S},4~{R},6~{a}~{R})-2,3,3~{a},4,5,6~{a}-hexahydrofuro[2,3-b]furan-4-yl]oxycarbonylamino]-2-oxidanyl-4-phenyl-butyl]-(2-methylpropyl)sulfamoyl]phenyl]-oxidanyl-oxidanylidene-boron'>BVR</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6c8x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c8x OCA], [http://pdbe.org/6c8x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c8x RCSB], [http://www.ebi.ac.uk/pdbsum/6c8x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c8x ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Boronic acids have been typecast as moieties for covalent complexation and are employed only rarely as agents for non-covalent recognition. By exploiting the profuse ability of a boronic acid group to form hydrogen bonds, we have developed an inhibitor of HIV-1 protease with extraordinary affinity. Specifically, we find that replacing an aniline moiety in darunavir with a phenylboronic acid leads to 20-fold greater affinity for the protease. X-ray crystallography demonstrates that the boronic acid group participates in three hydrogen bonds, more than the amino group of darunavir or any other analog. Importantly, the boronic acid maintains its hydrogen bonds and its affinity for the drug-resistant D30N variant of HIV-1 protease. The BOH...OC hydrogen bonds between the boronic acid hydroxy group and Asp30 (or Asn30) of the protease are short ( rO...O = 2.2 A), and density functional theory analysis reveals a high degree of covalency. These data highlight the utility of boronic acids as versatile functional groups in the design of small-molecule ligands. | ||
| - | + | Sub-picomolar Inhibition of HIV-1 Protease with a Boronic Acid.,Windsor IW, Palte MJ, Lukesh JC 3rd, Gold B, Forest KT, Raines RT J Am Chem Soc. 2018 Oct 31;140(43):14015-14018. doi: 10.1021/jacs.8b07366. Epub, 2018 Oct 22. PMID:30346745<ref>PMID:30346745</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6c8x" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Forest, K T]] | ||
| + | [[Category: Raines, R T]] | ||
| + | [[Category: Windsor, I W]] | ||
| + | [[Category: Boronic acid]] | ||
| + | [[Category: Hiv]] | ||
| + | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Protease]] | ||
Revision as of 06:33, 5 December 2018
Wild-type HIV-1 protease in complex with a phenylboronic acid (P2') analog of darunavir
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