6ogl

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<StructureSection load='6ogl' size='340' side='right'caption='[[6ogl]], [[Resolution|resolution]] 1.21&Aring;' scene=''>
<StructureSection load='6ogl' size='340' side='right'caption='[[6ogl]], [[Resolution|resolution]] 1.21&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6ogl]] is a 1 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=6OGL FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6ogl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. 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 [https://proteopedia.org/fgij/fg.htm?mol=6OGL FirstGlance]. <br>
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</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>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.21&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pol ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</td></tr>
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<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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ogl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ogl OCA], [https://pdbe.org/6ogl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ogl RCSB], [https://www.ebi.ac.uk/pdbsum/6ogl PDBsum], [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=6ogl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ogl OCA], [https://pdbe.org/6ogl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ogl RCSB], [https://www.ebi.ac.uk/pdbsum/6ogl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ogl ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/A0A4P8EW36_9HIV1 A0A4P8EW36_9HIV1]
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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.
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6ogl" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Aoki, M]]
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[[Category: Aoki M]]
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[[Category: Aoki-Ogata, H]]
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[[Category: Aoki-Ogata H]]
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[[Category: Bulut, H]]
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[[Category: Bulut H]]
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[[Category: Ghosh, A K]]
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[[Category: Ghosh AK]]
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[[Category: Hattori, S I]]
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[[Category: Hattori SI]]
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[[Category: Hayashi, H]]
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[[Category: Hayashi H]]
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[[Category: Mitsuya, H]]
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[[Category: Mitsuya H]]
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[[Category: Inhibitor]]
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[[Category: Viral protein]]
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[[Category: Viral protein-inhibitor complex]]
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Current revision

X-ray crystal structure of darunavir-resistant HIV-1 protease (P51) in complex with GRL-003

PDB ID 6ogl

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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