7myy
From Proteopedia
(Difference between revisions)
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==Crystal Structure of HIV-1 PRS17 with GRL-142== | ==Crystal Structure of HIV-1 PRS17 with GRL-142== | ||
| - | <StructureSection load='7myy' size='340' side='right'caption='[[7myy]]' scene=''> | + | <StructureSection load='7myy' size='340' side='right'caption='[[7myy]], [[Resolution|resolution]] 1.50Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MYY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MYY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7myy]] 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=7MYY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MYY FirstGlance]. <br> |
| - | </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=7myy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7myy OCA], [https://pdbe.org/7myy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7myy RCSB], [https://www.ebi.ac.uk/pdbsum/7myy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7myy ProSAT]</span></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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7OA:(3S,3aR,5R,7aS,8S)-hexahydro-4H-3,5-methanofuro[2,3-b]pyran-8-yl+[(2S,3R)-4-[{[2-(cyclopropylamino)-1,3-benzothiazol-6-yl]sulfonyl}(2-methylpropyl)amino]-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl]carbamate'>7OA</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'>[https://proteopedia.org/fgij/fg.htm?mol=7myy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7myy OCA], [https://pdbe.org/7myy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7myy RCSB], [https://www.ebi.ac.uk/pdbsum/7myy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7myy ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/I7BFC3_9HIV1 I7BFC3_9HIV1] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The emergence of multidrug resistant (MDR) HIV strains severely reduces the effectiveness of antiretroviral therapy. Clinical inhibitor darunavir (1) has picomolar binding affinity for HIV-1 protease (PR), however, drug resistant variants like PR(S17) show poor inhibition by 1, despite the presence of only two mutated residues in the inhibitor-binding site. Antiviral inhibitors that target MDR proteases like PR(S17) would be valuable as therapeutic agents. Inhibitors 2 and 3 derived from 1 through substitutions at P1, P2 and P2' positions exhibit 3.4- to 500-fold better inhibition than clinical inhibitors for PR(S17) with the exception of amprenavir. Crystal structures of PR(S17)/2 and PR(S17)/3 reveal how these inhibitors target the two active site mutations of PR(S17). The substituted methoxy P2 group of 2 forms new interactions with G48V mutation, while the modified bis-fluoro-benzyl P1 group of 3 forms a halogen interaction with V82S mutation, contributing to improved inhibition of PR(S17). | ||
| + | |||
| + | Novel HIV PR inhibitors with C4-substituted bis-THF and bis-fluoro-benzyl target the two active site mutations of highly drug resistant mutant PR(S17).,Agniswamy J, Kneller DW, Ghosh AK, Weber IT Biochem Biophys Res Commun. 2021 Aug 20;566:30-35. doi:, 10.1016/j.bbrc.2021.05.094. Epub 2021 Jun 7. PMID:34111669<ref>PMID:34111669</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7myy" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Agniswamy J]] | [[Category: Agniswamy J]] | ||
[[Category: Weber IT]] | [[Category: Weber IT]] | ||
Current revision
Crystal Structure of HIV-1 PRS17 with GRL-142
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