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| | <SX load='6rwl' size='340' side='right' viewer='molstar' caption='[[6rwl]], [[Resolution|resolution]] 3.36Å' scene=''> | | <SX load='6rwl' size='340' side='right' viewer='molstar' caption='[[6rwl]], [[Resolution|resolution]] 3.36Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6rwl]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Civ Civ]. 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 [http://proteopedia.org/fgij/fg.htm?mol=6RWL FirstGlance]. <br> | + | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11723 CIV])</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'>[http://proteopedia.org/fgij/fg.htm?mol=6rwl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rwl OCA], [http://pdbe.org/6rwl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rwl RCSB], [http://www.ebi.ac.uk/pdbsum/6rwl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rwl 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=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> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/E1ANT8_SIV E1ANT8_SIV] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6rwl" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6rwl" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Retroviral integrase 3D structures|Retroviral integrase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Civ]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cherepanov, P]] | + | [[Category: Simian immunodeficiency virus]] |
| - | [[Category: Cook, N]] | + | [[Category: Cherepanov P]] |
| - | [[Category: Nans, A]] | + | [[Category: Cook N]] |
| - | [[Category: Lentivirus]] | + | [[Category: Nans A]] |
| - | [[Category: Protein-dna complex]]
| + | |
| - | [[Category: Recombination]]
| + | |
| - | [[Category: Retroviral integrase]]
| + | |
| - | [[Category: Strand transfer inhibior]]
| + | |
| Structural highlights
Function
E1ANT8_SIV
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cook NJ, Li W, Berta D, Badaoui M, Ballandras-Colas A, Nans A, Kotecha A, Rosta E, Engelman AN, Cherepanov P. Structural basis of second-generation HIV integrase inhibitor action and viral resistance. Science. 2020 Feb 14;367(6479):806-810. doi: 10.1126/science.aay4919. Epub 2020, Jan 30. PMID:32001525 doi:http://dx.doi.org/10.1126/science.aay4919
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