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==HIV-1 Integrase Catalytic Core Domain Complexed with Allosteric Inhibitor (2S)-tert-butoxy[3-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-phenylisoquinolin-4-yl]acetic acid== | ==HIV-1 Integrase Catalytic Core Domain Complexed with Allosteric Inhibitor (2S)-tert-butoxy[3-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-phenylisoquinolin-4-yl]acetic acid== | ||
<StructureSection load='6eb1' size='340' side='right' | <StructureSection load='6eb1' size='340' side='right'caption='[[6eb1]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6eb1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EB1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EB1 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6eb1]] is a 1 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=6EB1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EB1 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=J3M:(2S)-tert-butoxy[3-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-phenylisoquinolin-4-yl]acetic+acid'>J3M</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=J3M:(2S)-tert-butoxy[3-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-phenylisoquinolin-4-yl]acetic+acid'>J3M</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='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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pol ([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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6eb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eb1 OCA], [http://pdbe.org/6eb1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eb1 RCSB], [http://www.ebi.ac.uk/pdbsum/6eb1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eb1 ProSAT]</span></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=6eb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eb1 OCA], [http://pdbe.org/6eb1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eb1 RCSB], [http://www.ebi.ac.uk/pdbsum/6eb1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eb1 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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</div> | </div> | ||
<div class="pdbe-citations 6eb1" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6eb1" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Retroviral integrase 3D structures|Retroviral integrase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Kobe, M]] | [[Category: Kobe, M]] | ||
[[Category: Kvaratskhelia, M]] | [[Category: Kvaratskhelia, M]] | ||
Revision as of 13:30, 18 December 2019
HIV-1 Integrase Catalytic Core Domain Complexed with Allosteric Inhibitor (2S)-tert-butoxy[3-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-phenylisoquinolin-4-yl]acetic acidHIV-1 Integrase Catalytic Core Domain Complexed with Allosteric Inhibitor (2S)-tert-butoxy[3-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-phenylisoquinolin-4-yl]acetic acid
Structural highlights
Publication Abstract from PubMedAllosteric HIV-1 integrase inhibitors (ALLINIs) are a new class of potential antiretroviral therapies with a unique mechanism of action and drug resistance profile. To further extend this class of inhibitors via a scaffold hopping approach, we have synthesized a series of analogues possessing an isoquinoline ring system. Lead compound 6l binds in the v-shaped pocket at the IN dimer interface and is highly selective for promoting higher-order multimerization of inactive IN over inhibiting IN-LEDGF/p75 binding. Importantly, 6l potently inhibited HIV-1NL4-3 (A128T IN), which confers marked resistance to archetypal quinoline-based ALLINIs. Thermal degradation studies indicated that at elevated temperatures the acetic acid side chain of specific isoquinoline derivatives undergo decarboxylation reactions. This reactivity has implications for the synthesis of various ALLINI analogues. An Isoquinoline Scaffold as a Novel Class of Allosteric HIV-1 Integrase Inhibitors.,Wilson TA, Koneru PC, Rebensburg SV, Lindenberger JJ, Kobe MJ, Cockroft NT, Adu-Ampratwum D, Larue RC, Kvaratskhelia M, Fuchs JR ACS Med Chem Lett. 2019 Jan 30;10(2):215-220. doi:, 10.1021/acsmedchemlett.8b00633. eCollection 2019 Feb 14. PMID:30783506[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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