4zdz: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4zdz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_YJM789 Saccharomyces cerevisiae YJM789]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZDZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZDZ FirstGlance]. <br> | <table><tr><td colspan='2'>[[4zdz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_YJM789 Saccharomyces cerevisiae YJM789]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZDZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZDZ FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=TPF:2-(2,4-DIFLUOROPHENYL)-1,3-DI(1H-1,2,4-TRIAZOL-1-YL)PROPAN-2-OL'>TPF</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=TPF:2-(2,4-DIFLUOROPHENYL)-1,3-DI(1H-1,2,4-TRIAZOL-1-YL)PROPAN-2-OL'>TPF</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=4zdz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zdz OCA], [https://pdbe.org/4zdz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zdz RCSB], [https://www.ebi.ac.uk/pdbsum/4zdz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zdz 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=4zdz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zdz OCA], [https://pdbe.org/4zdz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zdz RCSB], [https://www.ebi.ac.uk/pdbsum/4zdz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zdz ProSAT]</span></td></tr> | ||
</table> | </table> | ||
Revision as of 11:16, 27 September 2023
Saccharomyces cerevisiae CYP51 (Lanosterol 14-alpha demethylase) Y140F mutant complexed with fluconazoleSaccharomyces cerevisiae CYP51 (Lanosterol 14-alpha demethylase) Y140F mutant complexed with fluconazole
Structural highlights
FunctionPublication Abstract from PubMedEmergence of fungal strains showing resistance to triazole drugs can make treatment of fungal disease problematic. Triazole resistance can arise due to single mutations in the drug target lanosterol 14alpha-demethylase (Erg11p/CYP51). We have determined how commonly occurring single site mutations in pathogenic fungi affect triazole binding using Saccharomyces cerevisiae Erg11p (ScErg11p) as a target surrogate. The mutations Y140F/H were introduced into full-length hexahistidine-tagged ScErg11p. Phenotypes and high-resolution X-ray crystal structures were determined for the mutant enzymes complexed with short-tailed (fluconazole and voriconazole) or long-tailed (itraconazole and posaconazole) triazoles and wild type enzyme complexed with voriconazole. The mutations disrupted a water-mediated hydrogen bond network involved in binding of short-tailed triazoles, which contain a tertiary hydroxyl not present in long-tailed triazoles. This appears to be the mechanism by which resistance to these short chain azoles occurs. Understanding how these mutations affect drug affinity will aid the design of azoles that overcome resistance. Triazole resistance mediated by mutations of a conserved active site tyrosine in fungal lanosterol 14alpha-demethylase.,Sagatova AA, Keniya MV, Wilson RK, Sabherwal M, Tyndall JD, Monk BC Sci Rep. 2016 May 18;6:26213. doi: 10.1038/srep26213. PMID:27188873[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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