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==Saccharomyces cerevisiae CYP51 (Lanosterol 14-alpha demethylase) Y140F mutant complexed with fluconazole==
==Saccharomyces cerevisiae CYP51 (Lanosterol 14-alpha demethylase) Y140F mutant complexed with fluconazole==
<StructureSection load='4zdz' size='340' side='right' caption='[[4zdz]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
<StructureSection load='4zdz' size='340' side='right'caption='[[4zdz]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4zdz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. 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 [http://oca.weizmann.ac.il/oca-docs/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"><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]] 2.3&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4k0f|4k0f]], [[4wmz|4wmz]], [[4zdy|4zdy]], [[4ze0|4ze0]], [[4ze1|4ze1]], [[4ze2|4ze2]], [[4ze3|4ze3]], [[4lxj|4lxj]]</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ERG11, SCY_2394 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=307796 Baker's yeast])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zdz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zdz OCA], [http://pdbe.org/4zdz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zdz RCSB], [http://www.ebi.ac.uk/pdbsum/4zdz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zdz ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/A6ZSR0_YEAS7 A6ZSR0_YEAS7]
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.


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>
==See Also==
 
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4zdz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Baker's yeast]]
[[Category: Large Structures]]
[[Category: Keniya, M V]]
[[Category: Saccharomyces cerevisiae YJM789]]
[[Category: Monk, B C]]
[[Category: Keniya MV]]
[[Category: Sagatova, A]]
[[Category: Monk BC]]
[[Category: Tyndall, J D.A]]
[[Category: Sagatova A]]
[[Category: Wilson, R K]]
[[Category: Tyndall JDA]]
[[Category: Cyp51]]
[[Category: Wilson RK]]
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
[[Category: Resistance mutation]]

Latest revision as of 17:07, 13 March 2024

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

4zdz is a 1 chain structure with sequence from Saccharomyces cerevisiae YJM789. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A6ZSR0_YEAS7

See Also

4zdz, resolution 2.30Å

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OCA
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