5eaf: Difference between revisions
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''' | ==Saccharomyces cerevisiae CYP51 complexed with the plant pathogen inhibitor Fluquinconazole== | ||
<StructureSection load='5eaf' size='340' side='right' caption='[[5eaf]], [[Resolution|resolution]] 2.65Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5eaf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EAF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EAF FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FQC:3-(2,4-DICHLOROPHENYL)-6-FLUORANYL-2-(1,2,4-TRIAZOL-1-YL)QUINAZOLIN-4-ONE'>FQC</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4wmz|4wmz]], [[5eab|5eab]], [[5eac|5eac]], [[5ead|5ead]], [[5eae|5eae]], [[5eag|5eag]], [[5eah|5eah]]</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=5eaf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eaf OCA], [http://pdbe.org/5eaf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eaf RCSB], [http://www.ebi.ac.uk/pdbsum/5eaf PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5eaf" style="background-color:#fffaf0;"></div> | |||
== References == | |||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: Keniya, M V]] | |||
[[Category: Monk, B C]] | |||
[[Category: Sabherwal, M]] | [[Category: Sabherwal, M]] | ||
[[Category: | [[Category: Sagatova, A A]] | ||
[[Category: | [[Category: Tyndall, J D.A]] | ||
[[Category: | [[Category: Wilson, R K]] | ||
[[Category: | [[Category: Woods, M V]] | ||
[[Category: Cyp51]] | |||
[[Category: Fluquinconazole]] | |||
[[Category: Oxidoreductase-oxidoreducatse inhibitor complex]] | |||
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | |||
Revision as of 20:15, 10 February 2016
Saccharomyces cerevisiae CYP51 complexed with the plant pathogen inhibitor FluquinconazoleSaccharomyces cerevisiae CYP51 complexed with the plant pathogen inhibitor Fluquinconazole
Structural highlights
Publication Abstract from PubMedInfections 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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