View source for 5eqb


==Crystal structure of lanosterol 14-alpha demethylase with intact transmembrane domain bound to itraconazole==
<StructureSection load='5eqb' size='340' side='right'caption='[[5eqb]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5eqb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EQB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EQB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.19&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5eqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eqb OCA], [https://pdbe.org/5eqb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5eqb RCSB], [https://www.ebi.ac.uk/pdbsum/5eqb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5eqb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CP51_YEAST CP51_YEAST] Catalyzes C14-demethylation of lanosterol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae S288C]]
[[Category: Cannon RD]]
[[Category: Finer-Morre J]]
[[Category: Huschmann FU]]
[[Category: Keniya MV]]
[[Category: Monk BC]]
[[Category: O'Connell III JD]]
[[Category: Stroud RM]]
[[Category: Tomasiak TM]]
[[Category: Tyndall JDA]]