6nuj
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==HIV-1 Integrase Catalytic Core Domain Complexed with Allosteric Inhibitor BI-224436== | |
| + | <StructureSection load='6nuj' size='340' side='right'caption='[[6nuj]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6nuj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NUJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NUJ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L3D:(2S)-tert-butoxy[4-(2,3-dihydropyrano[4,3,2-de]quinolin-7-yl)-2-methylquinolin-3-yl]acetic+acid'>L3D</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAF:S-DIMETHYLARSINOYL-CYSTEINE'>CAF</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=6nuj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nuj OCA], [http://pdbe.org/6nuj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nuj RCSB], [http://www.ebi.ac.uk/pdbsum/6nuj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nuj ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are a promising new class of antiretroviral agents that disrupt proper viral maturation by inducing hyper-multimerization of IN. Here we show that lead pyridine-based ALLINI KF116 exhibits striking selectivity for IN tetramers versus lower order protein oligomers. IN structural features that are essential for its functional tetramerization and HIV-1 replication are also critically important for KF116 mediated higher-order IN multimerization. Live cell imaging of single viral particles revealed that KF116 treatment during virion production compromises the tight association of IN with capsid cores during subsequent infection of target cells. We have synthesized the highly active (-)-KF116 enantiomer, which displayed EC50 of ~7 nM against wild type HIV-1 and ~10 fold higher, sub-nM activity against a clinically relevant dolutegravir resistant mutant virus suggesting potential clinical benefits for complementing dolutegravir therapy with pyridine-based ALLINIs. | ||
| - | + | HIV-1 integrase tetramers are the antiviral target of pyridine-based allosteric integrase inhibitors.,Koneru PC, Francis AC, Deng N, Rebensburg SV, Hoyte AC, Lindenberger J, Adu-Ampratwum D, Larue RC, Wempe MF, Engelman AN, Lyumkis D, Fuchs JR, Levy RM, Melikyan GB, Kvaratskhelia M Elife. 2019 May 23;8. pii: 46344. doi: 10.7554/eLife.46344. PMID:31120420<ref>PMID:31120420</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | [[Category: | + | <div class="pdbe-citations 6nuj" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Kvaratskhelia, M]] | [[Category: Kvaratskhelia, M]] | ||
| + | [[Category: Lindenberger, J J]] | ||
| + | [[Category: Allosteric]] | ||
| + | [[Category: Hiv]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Integrase]] | ||
| + | [[Category: Transferase-transferase inhibitor complex]] | ||
Revision as of 15:08, 11 December 2019
HIV-1 Integrase Catalytic Core Domain Complexed with Allosteric Inhibitor BI-224436
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