6rwl: Difference between revisions
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==SIVrcm intasome== | |||
<SX load='6rwl' size='340' side='right' viewer='molstar' caption='[[6rwl]], [[Resolution|resolution]] 3.36Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6rwl]] 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=6RWL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RWL 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]] 3.36Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=6rwl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rwl OCA], [https://pdbe.org/6rwl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rwl RCSB], [https://www.ebi.ac.uk/pdbsum/6rwl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rwl 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 6rwl" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Retroviral integrase 3D structures|Retroviral integrase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</SX> | |||
[[Category: Large Structures]] | |||
[[Category: Simian immunodeficiency virus]] | |||
[[Category: Cherepanov P]] | |||
[[Category: Cook N]] | |||
[[Category: Nans A]] | |||
Latest revision as of 08:52, 14 July 2024
SIVrcm intasome
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