6ogp
From Proteopedia
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<StructureSection load='6ogp' size='340' side='right'caption='[[6ogp]], [[Resolution|resolution]] 1.53Å' scene=''> | <StructureSection load='6ogp' size='340' side='right'caption='[[6ogp]], [[Resolution|resolution]] 1.53Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6ogp]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OGP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6OGP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ogp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OGP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6OGP FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MJD:(3S,3aR,5R,7aS,8S)-hexahydro-4H-3,5-methanofuro[2,3-b]pyran-8-yl+{(2S,3R)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(2-methylpropyl)({2-[(propan-2-yl)amino]-1,3-benzoxazol-6-yl}sulfonyl)amino]butan-2-yl}carbamate'>MJD</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MJD:(3S,3aR,5R,7aS,8S)-hexahydro-4H-3,5-methanofuro[2,3-b]pyran-8-yl+{(2S,3R)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(2-methylpropyl)({2-[(propan-2-yl)amino]-1,3-benzoxazol-6-yl}sulfonyl)amino]butan-2-yl}carbamate'>MJD</scene></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=11676 9HIV1])</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=6ogp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ogp OCA], [http://pdbe.org/6ogp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ogp RCSB], [http://www.ebi.ac.uk/pdbsum/6ogp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ogp ProSAT]</span></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=6ogp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ogp OCA], [http://pdbe.org/6ogp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ogp RCSB], [http://www.ebi.ac.uk/pdbsum/6ogp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ogp ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | HIV-1 protease inhibitors (PIs), such as darunavir (DRV), are the key component of antiretroviral therapy. However, HIV-1 often acquires resistance to PIs. Here, seven novel PIs were synthesized, by introducing single atom changes such as an exchange of a sulfur to an oxygen, scission of a single bond in P2'-cyclopropylaminobenzothiazole (or -oxazole), and/or P1-benzene ring with fluorine scan of mono- or bis-fluorine atoms around DRV's scaffold. X-ray structural analyses of the PIs complexed with wild-type Protease (PRWT) and highly-multi-PI-resistance-associated PRDRV(R)P51 revealed that the PIs better adapt to structural plasticity in PR with resistance-associated amino acid substitutions by formation of optimal sulfur bond and adaptation of cyclopropyl ring in the S2'-subsite. Furthermore, these PIs displayed increased cell permeability and extreme anti-HIV-1 potency compared to DRV. Our work provides the basis for developing novel PIs with high potency against PI-resistant HIV-1 variants with a high genetic barrier. | ||
| + | |||
| + | Single atom changes in newly synthesized HIV protease inhibitors reveal structural basis for extreme affinity, high genetic barrier, and adaptation to the HIV protease plasticity.,Bulut H, Hattori SI, Aoki-Ogata H, Hayashi H, Das D, Aoki M, Davis DA, Rao KV, Nyalapatla PR, Ghosh AK, Mitsuya H Sci Rep. 2020 Jun 30;10(1):10664. doi: 10.1038/s41598-020-65993-z. PMID:32606378<ref>PMID:32606378</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6ogp" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 11:23, 26 August 2020
X-ray crystal structure of wild type HIV-1 protease in complex with GRL-063
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