6vkv
From Proteopedia
(Difference between revisions)
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==Co-crystal structure of GS-6207 bound to HIV-1 capsid hexamer== | ==Co-crystal structure of GS-6207 bound to HIV-1 capsid hexamer== | ||
| - | <StructureSection load='6vkv' size='340' side='right'caption='[[6vkv]]' scene=''> | + | <StructureSection load='6vkv' size='340' side='right'caption='[[6vkv]], [[Resolution|resolution]] 2.22Å' 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=6VKV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VKV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6vkv]] is a 3 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=6VKV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VKV FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vkv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vkv OCA], [http://pdbe.org/6vkv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vkv RCSB], [http://www.ebi.ac.uk/pdbsum/6vkv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vkv ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=QNG:N-[(1S)-1-(3-{4-chloro-3-[(methylsulfonyl)amino]-1-(2,2,2-trifluoroethyl)-1H-indazol-7-yl}-6-[3-methyl-3-(methylsulfonyl)but-1-yn-1-yl]pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl]-2-[(3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl]acetamide'>QNG</scene></td></tr> |
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6vws|6vws]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gag ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vkv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vkv OCA], [http://pdbe.org/6vkv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vkv RCSB], [http://www.ebi.ac.uk/pdbsum/6vkv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vkv ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The potent HIV-1 capsid inhibitor GS-6207 is an investigational principal component of long-acting antiretroviral therapy. We found that GS-6207 inhibits HIV-1 by stabilizing and thereby preventing functional disassembly of the capsid shell in infected cells. X-ray crystallography, cryo-electron microscopy, and hydrogen-deuterium exchange experiments revealed that GS-6207 tightly binds two adjoining capsid subunits and promotes distal intra- and inter-hexamer interactions that stabilize the curved capsid lattice. In addition, GS-6207 interferes with capsid binding to the cellular HIV-1 cofactors Nup153 and CPSF6 that mediate viral nuclear import and direct integration into gene-rich regions of chromatin. These findings elucidate structural insights into the multimodal, potent antiviral activity of GS-6207 and provide a means for rationally developing second-generation therapies. | ||
| + | |||
| + | Structural and mechanistic bases for a potent HIV-1 capsid inhibitor.,Bester SM, Wei G, Zhao H, Adu-Ampratwum D, Iqbal N, Courouble VV, Francis AC, Annamalai AS, Singh PK, Shkriabai N, Van Blerkom P, Morrison J, Poeschla EM, Engelman AN, Melikyan GB, Griffin PR, Fuchs JR, Asturias FJ, Kvaratskhelia M Science. 2020 Oct 16;370(6514):360-364. doi: 10.1126/science.abb4808. PMID:33060363<ref>PMID:33060363</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6vkv" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Bester | + | [[Category: Bester, S M]] |
| - | [[Category: Kvaratskhelia M]] | + | [[Category: Kvaratskhelia, M]] |
| + | [[Category: Viral protein]] | ||
Revision as of 07:36, 4 November 2020
Co-crystal structure of GS-6207 bound to HIV-1 capsid hexamer
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