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==Saccharomyces cerevisiae CYP51 (Lanosterol 14-alpha demethylase) G73W mutant in complex with itraconazole== | |||
<StructureSection load='5esh' size='340' side='right' caption='[[5esh]], [[Resolution|resolution]] 2.15Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5esh]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ESH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ESH 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">[[5ese|5ese]], [[5esf|5esf]], [[5esg|5esg]], [[5esi|5esi]], [[5esj|5esj]], [[5esk|5esk]], [[5esl|5esl]], [[5esm|5esm]], [[5esn|5esn]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Sterol_14-demethylase Sterol 14-demethylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.70 1.14.13.70] </span></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=5esh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5esh OCA], [http://pdbe.org/5esh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5esh RCSB], [http://www.ebi.ac.uk/pdbsum/5esh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5esh ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Bitopic integral membrane proteins with a single transmembrane helix play diverse roles in catalysis, cell signaling, and morphogenesis. Complete monospanning protein structures are needed to show how interaction between the transmembrane helix and catalytic domain might influence association with the membrane and function. We report crystal structures of full-length Saccharomyces cerevisiae lanosterol 14alpha-demethylase, a membrane monospanning cytochrome P450 of the CYP51 family that catalyzes the first postcyclization step in ergosterol biosynthesis and is inhibited by triazole drugs. The structures reveal a well-ordered N-terminal amphipathic helix preceding a putative transmembrane helix that would constrain the catalytic domain orientation to lie partly in the lipid bilayer. The structures locate the substrate lanosterol, identify putative substrate and product channels, and reveal constrained interactions with triazole antifungal drugs that are important for drug design and understanding drug resistance. | |||
Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer.,Monk BC, Tomasiak TM, Keniya MV, Huschmann FU, Tyndall JD, O'Connell JD 3rd, Cannon RD, McDonald JG, Rodriguez A, Finer-Moore JS, Stroud RM Proc Natl Acad Sci U S A. 2014 Mar 11;111(10):3865-70. doi:, 10.1073/pnas.1324245111. Epub 2014 Feb 3. PMID:24613931<ref>PMID:24613931</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5esh" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Sterol 14-demethylase]] | |||
[[Category: Keniya, M V]] | |||
[[Category: Monk, B C]] | |||
[[Category: Sabherwal, M]] | [[Category: Sabherwal, M]] | ||
[[Category: Sagatova, A]] | [[Category: Sagatova, A]] | ||
[[Category: | [[Category: Tyndall, J D.A]] | ||
[[Category: | [[Category: Wilson, R K]] | ||
[[Category: Cyp51]] | |||
[[Category: Mutation]] | |||
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | |||
Revision as of 13:49, 10 December 2016
Saccharomyces cerevisiae CYP51 (Lanosterol 14-alpha demethylase) G73W mutant in complex with itraconazoleSaccharomyces cerevisiae CYP51 (Lanosterol 14-alpha demethylase) G73W mutant in complex with itraconazole
Structural highlights
Publication Abstract from PubMedBitopic integral membrane proteins with a single transmembrane helix play diverse roles in catalysis, cell signaling, and morphogenesis. Complete monospanning protein structures are needed to show how interaction between the transmembrane helix and catalytic domain might influence association with the membrane and function. We report crystal structures of full-length Saccharomyces cerevisiae lanosterol 14alpha-demethylase, a membrane monospanning cytochrome P450 of the CYP51 family that catalyzes the first postcyclization step in ergosterol biosynthesis and is inhibited by triazole drugs. The structures reveal a well-ordered N-terminal amphipathic helix preceding a putative transmembrane helix that would constrain the catalytic domain orientation to lie partly in the lipid bilayer. The structures locate the substrate lanosterol, identify putative substrate and product channels, and reveal constrained interactions with triazole antifungal drugs that are important for drug design and understanding drug resistance. Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer.,Monk BC, Tomasiak TM, Keniya MV, Huschmann FU, Tyndall JD, O'Connell JD 3rd, Cannon RD, McDonald JG, Rodriguez A, Finer-Moore JS, Stroud RM Proc Natl Acad Sci U S A. 2014 Mar 11;111(10):3865-70. doi:, 10.1073/pnas.1324245111. Epub 2014 Feb 3. PMID:24613931[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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