4ze2: Difference between revisions

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-'''Unreleased structure'''
-The entry 4ze2 is ON HOLD  until Paper Publication
+==Saccharomyces cerevisiae CYP51 (Lanosterol 14-alpha demethylase) Y140H mutant complexed with itraconazole==
+<StructureSection load='4ze2' size='340' side='right'caption='[[4ze2]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4ze2]] 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=4ZE2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZE2 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1YN:2-[(2R)-BUTAN-2-YL]-4-{4-[4-(4-{[(2R,4S)-2-(2,4-DICHLOROPHENYL)-2-(1H-1,2,4-TRIAZOL-1-YLMETHYL)-1,3-DIOXOLAN-4-YL]METHOXY}PHENYL)PIPERAZIN-1-YL]PHENYL}-2,4-DIHYDRO-3H-1,2,4-TRIAZOL-3-ONE'>1YN</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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=4ze2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ze2 OCA], [https://pdbe.org/4ze2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ze2 RCSB], [https://www.ebi.ac.uk/pdbsum/4ze2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ze2 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/A6ZSR0_YEAS7 A6ZSR0_YEAS7]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Emergence 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.
-Authors: Sagatova, A., Keniya, M.V., Wilson, R., Monk, B.C., Tyndall, J.D.A.
+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<ref>PMID:27188873</ref>
-Description: Saccharomyces cerevisiae CYP51 (Lanosterol 14-alpha demethylase) Y140H mutant complexed with itraconazole
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Sagatova, A]]
+<div class="pdbe-citations 4ze2" style="background-color:#fffaf0;"></div>
-[[Category: Tyndall, J.D.A]]
-[[Category: Monk, B.C]]
+==See Also==
-[[Category: Keniya, M.V]]
+*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
-[[Category: Wilson, R]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Saccharomyces cerevisiae YJM789]]
+[[Category: Keniya MV]]
+[[Category: Monk BC]]
+[[Category: Sagatova A]]
+[[Category: Tyndall JDA]]
+[[Category: Wilson R]]