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==Saccharomyces cerevisiae CYP51 (Lanosterol 14-alpha demethylase) G464S mutant complexed with itraconazole==
==Saccharomyces cerevisiae CYP51 (Lanosterol 14-alpha demethylase) G464S mutant complexed with itraconazole==
<StructureSection load='5esk' size='340' side='right' caption='[[5esk]], [[Resolution|resolution]] 2.24&Aring;' scene=''>
<StructureSection load='5esk' size='340' side='right'caption='[[5esk]], [[Resolution|resolution]] 2.24&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5esk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ESK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ESK FirstGlance]. <br>
<table><tr><td colspan='2'>[[5esk]] 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=5ESK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ESK FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.24&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ese|5ese]], [[5esf|5esf]], [[5esj|5esj]], [[5esl|5esl]], [[5esm|5esm]], [[5esn|5esn]], [[5esg|5esg]], [[5esh|5esh]], [[5esi|5esi]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5esk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5esk OCA], [http://pdbe.org/5esk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5esk RCSB], [http://www.ebi.ac.uk/pdbsum/5esk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5esk 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=5esk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5esk OCA], [https://pdbe.org/5esk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5esk RCSB], [https://www.ebi.ac.uk/pdbsum/5esk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5esk 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]
Infections by fungal pathogens such as Candida albicans and Aspergillus fumigatus and their resistance to triazole drugs are major concerns. Fungal lanosterol 14alpha-demethylase belongs to the CYP51 class in the cytochrome P450 superfamily of enzymes. This monospanning bitopic membrane protein is involved in ergosterol biosynthesis and is the primary target of azole antifungal drugs, including fluconazole. The lack of high resolution structural information for this drug target from fungal pathogens has been a limiting factor for the design of modified triazole drugs that will overcome resistance. Here we report the X-ray structure of full-length Saccharomyces cerevisiae lanosterol 14alpha-demethylase in complex with fluconazole at a resolution of 2.05 A. This structure shows the key interactions involved in fluconazole binding and provides insight into resistance mechanisms by revealing a water mediated hydrogen bonding network between the drug and Tyrosine140, a residue frequently found mutated to histidine or phenylalanine in resistant clinical isolates.


Structural insights into binding of the antifungal drug fluconazole to Saccharomyces cerevisiae lanosterol 14alpha-demethylase.,Sagatova A, Keniya MV, Wilson RK, Monk BC, Tyndall JD Antimicrob Agents Chemother. 2015 Jun 8. pii: AAC.00925-15. PMID:26055382<ref>PMID:26055382</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 5esk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Keniya, M V]]
[[Category: Large Structures]]
[[Category: Monk, B C]]
[[Category: Saccharomyces cerevisiae YJM789]]
[[Category: Sabherwal, M]]
[[Category: Keniya MV]]
[[Category: Sagatova, A]]
[[Category: Monk BC]]
[[Category: Tyndall, J D.A]]
[[Category: Sabherwal M]]
[[Category: Wilson, R K]]
[[Category: Sagatova A]]
[[Category: Cyp51]]
[[Category: Tyndall JDA]]
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
[[Category: Wilson RK]]
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