This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
6ogl
From Proteopedia
(Difference between revisions)
| Line 3: | Line 3: | ||
<StructureSection load='6ogl' size='340' side='right'caption='[[6ogl]], [[Resolution|resolution]] 1.21Å' scene=''> | <StructureSection load='6ogl' size='340' side='right'caption='[[6ogl]], [[Resolution|resolution]] 1.21Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6ogl]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OGL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6OGL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ogl]] 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=6OGL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6OGL 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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JDV:(3S,3aR,5R,7aS,8S)-hexahydro-4H-3,5-methanofuro[2,3-b]pyran-8-yl+[(2S,3R)-4-[{[2-(cyclopropylamino)-1,3-benzothiazol-6-yl]sulfonyl}(2-methylpropyl)amino]-1-(4-fluorophenyl)-3-hydroxybutan-2-yl]carbamate'>JDV</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JDV:(3S,3aR,5R,7aS,8S)-hexahydro-4H-3,5-methanofuro[2,3-b]pyran-8-yl+[(2S,3R)-4-[{[2-(cyclopropylamino)-1,3-benzothiazol-6-yl]sulfonyl}(2-methylpropyl)amino]-1-(4-fluorophenyl)-3-hydroxybutan-2-yl]carbamate'>JDV</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=6ogl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ogl OCA], [http://pdbe.org/6ogl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ogl RCSB], [http://www.ebi.ac.uk/pdbsum/6ogl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ogl 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=6ogl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ogl OCA], [http://pdbe.org/6ogl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ogl RCSB], [http://www.ebi.ac.uk/pdbsum/6ogl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ogl 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 6ogl" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 11:23, 26 August 2020
X-ray crystal structure of darunavir-resistant HIV-1 protease (P51) in complex with GRL-003
| |||||||||||
