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| | ==Saccharomyces cerevisiae CYP51 complexed with the plant pathogen inhibitor Prochloraz== | | ==Saccharomyces cerevisiae CYP51 complexed with the plant pathogen inhibitor Prochloraz== |
| - | <StructureSection load='5eag' size='340' side='right' caption='[[5eag]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='5eag' size='340' side='right'caption='[[5eag]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5eag]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EAG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EAG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5eag]] 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=5EAG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EAG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5LU:PROCHLORAZ'>5LU</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]] 2.4Å</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]], [[5eaf|5eaf]], [[5eah|5eah]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5LU:PROCHLORAZ'>5LU</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=5eag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eag OCA], [http://pdbe.org/5eag PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eag RCSB], [http://www.ebi.ac.uk/pdbsum/5eag PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5eag 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=5eag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eag OCA], [https://pdbe.org/5eag PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5eag RCSB], [https://www.ebi.ac.uk/pdbsum/5eag PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5eag ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A6ZSR0_YEAS7 A6ZSR0_YEAS7] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5eag" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5eag" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]] |
| | == References == | | == References == |
| | <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 A]] | + | [[Category: Monk BC]] |
| - | [[Category: Tyndall, J D.A]] | + | [[Category: Sabherwal M]] |
| - | [[Category: Wilson, R K]]
| + | [[Category: Sagatova AA]] |
| - | [[Category: Woods, M V]]
| + | [[Category: Tyndall JDA]] |
| - | [[Category: Cyp51]] | + | [[Category: Wilson RK]] |
| - | [[Category: Oxidoreductase-oxidoreducatse inhibitor complex]] | + | [[Category: Woods MV]] |
| - | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | + | |
| - | [[Category: Prochloraz]] | + | |
| Structural highlights
Function
A6ZSR0_YEAS7
Publication Abstract from PubMed
Azole antifungals, known as demethylase inhibitors (DMIs), target sterol 14alpha-demethylase (CYP51) in the ergosterol biosynthetic pathway of fungal pathogens of both plants and humans. DMIs remain the treatment of choice in crop protection against a wide range of fungal phytopathogens that have the potential to reduce crop yields and threaten food security. We used a yeast membrane protein expression system to overexpress recombinant hexahistidine-tagged S. cerevisiae lanosterol 14alpha-demethylase and the Y140F or Y140H mutants of this enzyme as surrogates in order characterize interactions with DMIs. The whole-cell antifungal activity (MIC50 values) of both the R- and S-enantiomers of tebuconazole, prothioconazole (PTZ), prothioconazole-desthio, and oxo-prothioconazole (oxo-PTZ) as well as for fluquinconazole, prochloraz and a racemic mixture of difenoconazole were determined. In vitro binding studies with the affinity purified enzyme were used to show tight type II binding to the yeast enzyme for all compounds tested except PTZ and oxo-PTZ. High resolution X-ray crystal structures of ScErg11p6xHis in complex with seven DMIs, including four enantiomers, reveal triazole-mediated coordination of all compounds and the specific orientation of compounds within the relatively hydrophobic binding site. Comparison with CYP51 structures from fungal pathogens including Candida albicans, Candida glabrata and Aspergillus fumigatus provides strong evidence for a highly conserved CYP51 structure including the drug binding site. The structures obtained using S. cerevisiae lanosterol 14alpha-demethylase in complex with these agrochemicals provide the basis for understanding the impact of mutations on azole susceptibility and a platform for the structure-directed design of the next-generation of DMIs.
Structural and Functional Elucidation of Yeast Lanosterol 14alpha-Demethylase in Complex with Agrochemical Antifungals.,Tyndall JD, Sabherwal M, Sagatova AA, Keniya MV, Negroni J, Wilson RK, Woods MA, Tietjen K, Monk BC PLoS One. 2016 Dec 1;11(12):e0167485. doi: 10.1371/journal.pone.0167485., eCollection 2016. PMID:27907120[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tyndall JD, Sabherwal M, Sagatova AA, Keniya MV, Negroni J, Wilson RK, Woods MA, Tietjen K, Monk BC. Structural and Functional Elucidation of Yeast Lanosterol 14alpha-Demethylase in Complex with Agrochemical Antifungals. PLoS One. 2016 Dec 1;11(12):e0167485. doi: 10.1371/journal.pone.0167485., eCollection 2016. PMID:27907120 doi:http://dx.doi.org/10.1371/journal.pone.0167485
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