View source for 6eb2


==HIV-1 Integrase Catalytic Core Domain Complexed with Allosteric Inhibitor (2S)-[1-(1-benzyl-1H-pyrazol-4-yl)-3-(3,4-dihydro-2H-1-benzopyran-6-yl)isoquinolin-4-yl](tert-butoxy)acetic acid==
<StructureSection load='6eb2' size='340' side='right'caption='[[6eb2]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6eb2]] 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=6EB2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EB2 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.493&#8491;</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=J3P:(2S)-[1-(1-benzyl-1H-pyrazol-4-yl)-3-(3,4-dihydro-2H-1-benzopyran-6-yl)isoquinolin-4-yl](tert-butoxy)acetic+acid'>J3P</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=6eb2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eb2 OCA], [https://pdbe.org/6eb2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6eb2 RCSB], [https://www.ebi.ac.uk/pdbsum/6eb2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6eb2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/F2WR52_9HIV1 F2WR52_9HIV1] 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:30783506</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6eb2" style="background-color:#fffaf0;"></div>

==See Also==
*[[Retroviral integrase 3D structures|Retroviral integrase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Kobe M]]
[[Category: Kvaratskhelia M]]
[[Category: Lindenberger JJ]]