7ke0
From Proteopedia
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<StructureSection load='7ke0' size='340' side='right'caption='[[7ke0]], [[Resolution|resolution]] 2.19Å' scene=''> | <StructureSection load='7ke0' size='340' side='right'caption='[[7ke0]], [[Resolution|resolution]] 2.19Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'> | + | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KE0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KE0 FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.19Å</td></tr> |
| - | <tr id=' | + | <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=WBV:(2S)-tert-butoxy{4-(4-chlorophenyl)-2,3,6-trimethyl-1-[(1-methyl-1H-pyrazol-4-yl)methyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}acetic+acid'>WBV</scene></td></tr> |
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ke0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ke0 OCA], [https://pdbe.org/7ke0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ke0 RCSB], [https://www.ebi.ac.uk/pdbsum/7ke0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ke0 ProSAT]</span></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=7ke0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ke0 OCA], [https://pdbe.org/7ke0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ke0 RCSB], [https://www.ebi.ac.uk/pdbsum/7ke0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ke0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Allosteric integrase inhibitors (ALLINIs) are a class of experimental anti-HIV agents that target the noncatalytic sites of the viral integrase (IN) and interfere with the IN-viral RNA interaction during viral maturation. Here, we report a highly potent and safe pyrrolopyridine-based ALLINI, STP0404, displaying picomolar IC50 in human PBMCs with a >24,000 therapeutic index against HIV-1. X-ray structural and biochemical analyses revealed that STP0404 binds to the host LEDGF/p75 protein binding pocket of the IN dimer, which induces aberrant IN oligomerization and blocks the IN-RNA interaction. Consequently, STP0404 inhibits proper localization of HIV-1 RNA genomes in viral particles during viral maturation. Y99H and A128T mutations at the LEDGF/p75 binding pocket render resistance to STP0404. Extensive in vivo pharmacological and toxicity investigations demonstrate that STP0404 harbors outstanding therapeutic and safety properties. Overall, STP0404 is a potent and first-in-class ALLINI that targets LEDGF/p75 binding site and has advanced to a human trial. | ||
| - | + | ==See Also== | |
| - | + | *[[Retroviral integrase 3D structures|Retroviral integrase 3D structures]] | |
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | + | [[Category: Kvaratskhelia M]] | |
| - | [[Category: Kvaratskhelia | + | [[Category: Lindenberger JJ]] |
| - | [[Category: Lindenberger | + | |
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Current revision
HIV-1 Integrase catalytic core domain complexed with allosteric inhibitor STP03-0404
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