5t8h: Difference between revisions
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==Joint X-ray/neutron structure of HIV-1 protease triple mutant (V32I,I47V,V82I) with amprenavir at pH 6.0== | |||
<StructureSection load='5t8h' size='340' side='right' caption='[[5t8h]], [[Resolution|resolution]] 1.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5t8h]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T8H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T8H FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=478:{3-[(4-AMINO-BENZENESULFONYL)-ISOBUTYL-AMINO]-1-BENZYL-2-HYDROXY-PROPYL}-CARBAMIC+ACID+TETRAHYDRO-FURAN-3-YL+ESTER'>478</scene>, <scene name='pdbligand=DOD:DEUTERATED+WATER'>DOD</scene></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=5t8h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t8h OCA], [http://pdbe.org/5t8h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t8h RCSB], [http://www.ebi.ac.uk/pdbsum/5t8h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t8h ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
HIV-1 protease inhibitors are crucial for treatment of HIV-1/AIDS, but their effectiveness is thwarted by rapid emergence of drug resistance. To better understand binding of clinical inhibitors to resistant HIV-1 protease, we used room-temperature joint X-ray/neutron (XN) crystallography to obtain an atomic-resolution structure of the protease triple mutant (V32I/I47V/V82I) in complex with amprenavir. The XN structure reveals a D+ ion located midway between the inner Odelta1 oxygen atoms of the catalytic aspartic acid residues. Comparison of the current XN structure with our previous XN structure of the wild-type HIV-1 protease-amprenavir complex suggests that the three mutations do not significantly alter the drug-enzyme interactions. This is in contrast to the observations in previous 100 K X-ray structures of these complexes that indicated loss of interactions by the drug with the triple mutant protease. These findings, thus, uncover limitations of structural analysis of drug binding using X-ray structures obtained at 100 K. | |||
Room Temperature Neutron Crystallography of Drug Resistant HIV-1 Protease Uncovers Limitations of X-ray Structural Analysis at 100 K.,Gerlits O, Keen DA, Blakeley MP, Louis JM, Weber IT, Kovalevsky A J Med Chem. 2017 Feb 28. doi: 10.1021/acs.jmedchem.6b01767. PMID:28195728<ref>PMID:28195728</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Kovalevsky, A | <div class="pdbe-citations 5t8h" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Gerlits, O O]] | |||
[[Category: Kovalevsky, A Y]] | |||
[[Category: Aspartic protease drug resistant mutant amprenavir]] | |||
[[Category: Hydrolase-hydrolase inhibitor complex]] | |||
