4yoa: Difference between revisions
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<StructureSection load='4yoa' size='340' side='right' caption='[[4yoa]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='4yoa' size='340' side='right' caption='[[4yoa]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4yoa]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YOA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YOA FirstGlance]. <br> | <table><tr><td colspan='2'>[[4yoa]] 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=4YOA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YOA FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=017:(3R,3AS,6AR)-HEXAHYDROFURO[2,3-B]FURAN-3-YL(1S,2R)-3-[[(4-AMINOPHENYL)SULFONYL](ISOBUTYL)AMINO]-1-BENZYL-2-HYDROXYPROPYLCARBAMATE'>017</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=017:(3R,3AS,6AR)-HEXAHYDROFURO[2,3-B]FURAN-3-YL(1S,2R)-3-[[(4-AMINOPHENYL)SULFONYL](ISOBUTYL)AMINO]-1-BENZYL-2-HYDROXYPROPYLCARBAMATE'>017</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4yob|4yob]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4yob|4yob]]</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4yoa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yoa OCA], [http://pdbe.org/4yoa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yoa RCSB], [http://www.ebi.ac.uk/pdbsum/4yoa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yoa ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4yoa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yoa OCA], [http://pdbe.org/4yoa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yoa RCSB], [http://www.ebi.ac.uk/pdbsum/4yoa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yoa ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
HIV-1 protease (PR) is a 99 amino acid protein responsible for proteolytic processing of the viral polyprotein - an essential step in the HIV-1 life cycle. Drug resistance mutations in PR that are selected during antiretroviral therapy lead to reduced efficacy of protease inhibitors (PI) including darunavir (DRV). To identify the structural mechanisms associated with the DRV resistance mutation L33F, we performed X-ray crystallographic studies with a multi-drug resistant HIV-1 protease isolate that contains the L33F mutation (MDR769 L33F). In contrast to other PR L33F DRV complexes, the structure of MDR769 L33F complexed with DRV reported here displays the protease flaps in an open conformation. The L33F mutation increases noncovalent interactions in the hydrophobic pocket of the PR compared to the wild-type (WT) structure. As a result, L33F appears to act as a molecular anchor, reducing the flexibility of the 30s loop (residues 29-35) and the 80s loop (residues 79-84). Molecular anchoring of the 30s and 80s loops leaves an open S1/S1' subsite and distorts the conserved hydrogen-bonding network of DRV. These findings are consistent with previous reports despite structural differences with regards to flap conformation. | |||
The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops.,Kuiper BD, Keusch BJ, Dewdney TG, Chordia P, Ross K, Brunzelle JS, Kovari IA, MacArthur R, Salimnia H, Kovari LC Biochem Biophys Rep. 2015 Jun 12;2:160-165. doi: 10.1016/j.bbrep.2015.06.003., eCollection 2015 Jul. PMID:29124158<ref>PMID:29124158</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4yoa" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Immunodeficiency virus protease|Immunodeficiency virus protease]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
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[[Category: Darunavir]] | [[Category: Darunavir]] | ||
[[Category: Hiv-1 protease]] | [[Category: Hiv-1 protease]] | ||
[[Category: Hydrolase-hydrolase inhibitor complex]] | |||
[[Category: Hydrolase/hydrolase inhibitor]] | [[Category: Hydrolase/hydrolase inhibitor]] | ||