View source for 7ryx


==S. CEREVISIAE CYP51 COMPLEXED WITH VT-1129==
<StructureSection load='7ryx' size='340' side='right'caption='[[7ryx]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ryx]] 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=7RYX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RYX 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=81H:(2R)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-{5-[4-(trifluoromethoxy)phenyl]pyridin-2-yl}propan-2-ol'>81H</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=7ryx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ryx OCA], [https://pdbe.org/7ryx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ryx RCSB], [https://www.ebi.ac.uk/pdbsum/7ryx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ryx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CP51_YEAST CP51_YEAST] Catalyzes C14-demethylation of lanosterol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
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== Publication Abstract from PubMed ==
The fungal cytochrome P450 lanosterol 14alpha-demethylase (CYP51) is required for the biosynthesis of fungal-specific ergosterol and is the target of azole antifungal drugs. Despite proven success as a clinical target for azole antifungals, there is an urgent need to develop next-generation antifungals that target CYP51 to overcome the resistance of pathogenic fungi to existing azole drugs, toxic adverse reactions and drug interactions due to human drug-metabolizing CYPs. Candida parapsilosis is a readily transmitted opportunistic fungal pathogen that causes candidiasis in health care environments. In this study, we have characterised wild type C. parapsilosis CYP51 and its clinically significant, resistance-causing point mutation Y132F by expressing these enzymes in a Saccharomyces cerevisiae host system. In some cases, the enzymes were co-expressed with their cognate NADPH-cytochrome P450 reductase (CPR). Constitutive expression of CpCYP51 Y132F conferred a 10- to 12-fold resistance to fluconazole and voriconazole, reduced to ~6-fold resistance for the tetrazoles VT-1161 and VT-1129, but did not confer resistance to the long-tailed triazoles. Susceptibilities were unchanged in the case of CpCPR co-expression. Type II binding spectra showed tight triazole and tetrazole binding by affinity-purified recombinant CpCYP51. We report the X-ray crystal structure of ScCYP51 in complex with VT-1129 obtained at a resolution of 2.1 A. Structural analysis of azole-enzyme interactions and functional studies of recombinant CYP51 from C. parapsilosis have improved understanding of their susceptibility to azole drugs and will help advance structure-directed antifungal discovery.

Characterisation of Candida parapsilosis CYP51 as a Drug Target Using Saccharomyces cerevisiae as Host.,Ruma YN, Keniya MV, Tyndall JDA, Monk BC J Fungi (Basel). 2022 Jan 10;8(1). pii: jof8010069. doi: 10.3390/jof8010069. PMID:35050009<ref>PMID:35050009</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ryx" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae YJM789]]
[[Category: Keniya MV]]
[[Category: Monk BC]]
[[Category: Ruma YN]]
[[Category: Sagatova A]]
[[Category: Tyndall JD]]