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| | <StructureSection load='6eb1' size='340' side='right'caption='[[6eb1]], [[Resolution|resolution]] 2.20Å' scene=''> | | <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 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> | + | <table><tr><td colspan='2'>[[6eb1]] is a 1 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=6EB1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAF:S-DIMETHYLARSINOYL-CYSTEINE'>CAF</scene>, <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='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'>[https://proteopedia.org/fgij/fg.htm?mol=6eb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eb1 OCA], [https://pdbe.org/6eb1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6eb1 RCSB], [https://www.ebi.ac.uk/pdbsum/6eb1 PDBsum], [https://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> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/F2WR52_9HIV1 F2WR52_9HIV1] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Human immunodeficiency virus 1]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kobe, M]] | + | [[Category: Kobe M]] |
| - | [[Category: Kvaratskhelia, M]] | + | [[Category: Kvaratskhelia M]] |
| - | [[Category: Lindenberger, J J]] | + | [[Category: Lindenberger JJ]] |
| - | [[Category: Allosteric]]
| + | |
| - | [[Category: Hiv]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Integrase]]
| + | |
| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| Structural highlights
Function
F2WR52_9HIV1
Publication Abstract from PubMed
Allosteric 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 Also
References
- ↑ Wilson TA, Koneru PC, Rebensburg SV, Lindenberger JJ, Kobe MJ, Cockroft NT, Adu-Ampratwum D, Larue RC, Kvaratskhelia M, Fuchs JR. An Isoquinoline Scaffold as a Novel Class of Allosteric HIV-1 Integrase Inhibitors. ACS Med Chem Lett. 2019 Jan 30;10(2):215-220. doi:, 10.1021/acsmedchemlett.8b00633. eCollection 2019 Feb 14. PMID:30783506 doi:http://dx.doi.org/10.1021/acsmedchemlett.8b00633
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