4zdy

<StructureSection load='4zdy' size='340' side='right' caption='[[4zdy]], [[Resolution|resolution]] 2.02&Aring;' scene=''>

<table><tr><td colspan='2'>[[4zdy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZDY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZDY 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>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zdz|4zdz]], [[4ze0|4ze0]], [[4ze1|4ze1]], [[4ze2|4ze2]], [[4ze3|4ze3]]</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=4zdy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zdy OCA], [http://pdbe.org/4zdy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zdy RCSB], [http://www.ebi.ac.uk/pdbsum/4zdy PDBsum]</span></td></tr>

<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.

 

== References ==

[[Category: Keniya, M V]]

[[Category: Monk, B C]]

[[Category: Sagatova, A]]

[[Category: Tyndall, J D.A]]

[[Category: Wilson, R K]]

[[Category: Cyp51]]

[[Category: Itraconazole]]

[[Category: Resistance mutation]]