4ze3: Difference between revisions
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==Saccharomyces cerevisiae CYP51 (Lanosterol 14-alpha demethylase) Y140H mutant complexed with fluconazole== | |||
<StructureSection load='4ze3' size='340' side='right' caption='[[4ze3]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4ze3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZE3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZE3 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=TPF:2-(2,4-DIFLUOROPHENYL)-1,3-DI(1H-1,2,4-TRIAZOL-1-YL)PROPAN-2-OL'>TPF</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4k0f|4k0f]], [[4lxj|4lxj]], [[4wmz|4wmz]], [[4zdy|4zdy]], [[4zdz|4zdz]], [[4ze0|4ze0]], [[4ze1|4ze1]], [[4ze2|4ze2]]</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=4ze3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ze3 OCA], [http://pdbe.org/4ze3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ze3 RCSB], [http://www.ebi.ac.uk/pdbsum/4ze3 PDBsum]</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> | ||
<div class="pdbe-citations 4ze3" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Keniya, M V]] | |||
[[Category: Monk, B C]] | |||
[[Category: Sagatova, A]] | [[Category: Sagatova, A]] | ||
[[Category: Tyndall, J | [[Category: Tyndall, J D.A]] | ||
[[Category: Wilson, R]] | [[Category: Wilson, R]] | ||
[[Category: Cyp51]] | |||
[[Category: Fluconazole]] | |||
[[Category: Oxidoreductase-oxidoreducatse inhibitor complex]] | |||
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | |||
[[Category: Resistance mutation]] | |||
[[Category: Y140h]] | |||
Revision as of 23:27, 11 May 2016
Saccharomyces cerevisiae CYP51 (Lanosterol 14-alpha demethylase) Y140H mutant complexed with fluconazoleSaccharomyces cerevisiae CYP51 (Lanosterol 14-alpha demethylase) Y140H mutant complexed with fluconazole
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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