View source for 6rwm


==SIVrcm intasome in complex with bictegravir==
<SX load='6rwm' size='340' side='right' viewer='molstar' caption='[[6rwm]], [[Resolution|resolution]] 2.81&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6rwm]] 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=6RWM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RWM 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]] 2.81&#8491;</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=KLQ:Bictegravir'>KLQ</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=6rwm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rwm OCA], [https://pdbe.org/6rwm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rwm RCSB], [https://www.ebi.ac.uk/pdbsum/6rwm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rwm 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--&gt;histidine (Q148H) and glycine-140--&gt;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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6rwm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</SX>
[[Category: Large Structures]]
[[Category: Simian immunodeficiency virus]]
[[Category: Cherepanov P]]
[[Category: Cook N]]
[[Category: Nans A]]