6rwn
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==SIVrcm intasome in complex with dolutegravir== | |
| + | <SX load='6rwn' size='340' side='right' viewer='molstar' caption='[[6rwn]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6rwn]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Simian_immunodeficiency_virus Simian immunodeficiency virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RWN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RWN FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.1Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DLU:(4R,12AS)-N-(2,4-DIFLUOROBENZYL)-7-HYDROXY-4-METHYL-6,8-DIOXO-3,4,6,8,12,12A-HEXAHYDRO-2H-PYRIDO[1,2 4,5]PYRAZINO[2,1-B][1,3]OXAZINE-9-CARBOXAMIDE'>DLU</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6rwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rwn OCA], [https://pdbe.org/6rwn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rwn RCSB], [https://www.ebi.ac.uk/pdbsum/6rwn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rwn ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/E1ANT8_SIV E1ANT8_SIV] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Although second-generation HIV integrase strand-transfer inhibitors (INSTIs) are prescribed throughout the world, the mechanistic basis for the superiority of these drugs is poorly understood. We used single-particle cryo-electron microscopy to visualize the mode of action of the advanced INSTIs dolutegravir and bictegravir at near-atomic resolution. Glutamine-148-->histidine (Q148H) and glycine-140-->serine (G140S) amino acid substitutions in integrase that result in clinical INSTI failure perturb optimal magnesium ion coordination in the enzyme active site. The expanded chemical scaffolds of second-generation compounds mediate interactions with the protein backbone that are critical for antagonizing viruses containing the Q148H and G140S mutations. Our results reveal that binding to magnesium ions underpins a fundamental weakness of the INSTI pharmacophore that is exploited by the virus to engender resistance and provide a structural framework for the development of this class of anti-HIV/AIDS therapeutics. | ||
| - | + | Structural basis of second-generation HIV integrase inhibitor action and viral resistance.,Cook NJ, Li W, Berta D, Badaoui M, Ballandras-Colas A, Nans A, Kotecha A, Rosta E, Engelman AN, Cherepanov P Science. 2020 Feb 14;367(6479):806-810. doi: 10.1126/science.aay4919. Epub 2020, Jan 30. PMID:32001525<ref>PMID:32001525</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6rwn" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </SX> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Simian immunodeficiency virus]] | ||
| + | [[Category: Cherepanov P]] | ||
| + | [[Category: Cook N]] | ||
| + | [[Category: Nans A]] | ||
Current revision
SIVrcm intasome in complex with dolutegravir
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