View source for 6otg


==HIV-1 protease triple mutants V32I, I47V, V82I with GRL-011-11A (a methylamine bis-Tetrahydrofuran P2-Ligand, sulfonamide isostere derivate)==
<StructureSection load='6otg' size='340' side='right'caption='[[6otg]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6otg]] 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=6OTG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OTG FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4UY:(3R,3AS,4R,6AR)-4-(METHYLAMINO)HEXAHYDROFURO[2,3-B]FURAN-3-YL+[(2S,3R)-3-HYDROXY-4-{[(4-METHOXYPHENYL)SULFONYL](2-METHYLPROPYL)AMINO}-1-PHENYLBUTAN-2-YL]CARBAMATE'>4UY</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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'>[https://proteopedia.org/fgij/fg.htm?mol=6otg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6otg OCA], [https://pdbe.org/6otg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6otg RCSB], [https://www.ebi.ac.uk/pdbsum/6otg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6otg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q7SSI0_9HIV1 Q7SSI0_9HIV1] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
HIV-1 protease inhibitors are effective in HIV/AIDS therapy, although drug resistance is a severe problem. This study examines the effects of four investigational inhibitors against HIV-1 protease with drug resistant mutations of V32I, I47V and V82I (PRTri) that model the inhibitor-binding site of HIV-2 protease. These inhibitors contain diverse chemical modifications on the darunavir scaffold and form new interactions with wild type protease, however, the measured inhibition constants for PRTri mutant range from 17 to 40nM or significantly worse than picomolar values reported for wild type enzyme. The X-ray crystal structure of PRTri mutant in complex with inhibitor 1at 1.5A resolution shows minor changes in interactions with inhibitor compared with the corresponding wild type PR complex. Instead, the basic amine at P2 of inhibitor together with mutation V82I induces two alternate conformations for the side chain of Arg8 with new interactions with inhibitor and Leu10. Hence, inhibition is influenced by small coordinated changes in hydrophobic interactions.

Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I.,Pawar S, Wang YF, Wong-Sam A, Agniswamy J, Ghosh AK, Harrison RW, Weber IT Biochem Biophys Res Commun. 2019 May 12. pii: S0006-291X(19)30934-9. doi:, 10.1016/j.bbrc.2019.05.064. PMID:31092330<ref>PMID:31092330</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6otg" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Pawar S]]
[[Category: Wang Y-F]]
[[Category: Weber IT]]