5EQB

Crystal structure of lanosterol 14-alpha demethylase with intact transmembrane domain bound to itraconazole

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5EQB の概要

• エントリーDOI: 10.2210/pdb5eqb/pdb
• 分子名称: Lanosterol 14-alpha demethylase, PROTOPORPHYRIN IX CONTAINING FE, 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, ... (4 entities in total)
• 機能のキーワード: sterol antifungal membrane cytochrome, structural genomics, psi-2, protein structure initiative, center for structures of membrane proteins, csmp, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
• 細胞内の位置: Membrane; Single-pass membrane protein: P10614
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 63207.33

構造登録者

Monk, B.C.,Tomasiak, T.M.,Keniya, M.V.,Huschmann, F.U.,Tyndall, J.D.A.,O'Connell III, J.D.,Cannon, R.D.,Finer-Morre, J.,Stroud, R.M.,Center for Structures of Membrane Proteins (CSMP) (登録日: 2015-11-12, 公開日: 2016-01-13, 最終更新日: 2024-03-06)

主引用文献

Monk, B.C.,Tomasiak, T.M.,Keniya, M.V.,Huschmann, F.U.,Tyndall, J.D.,O'Connell, J.D.,Cannon, R.D.,McDonald, J.G.,Rodriguez, A.,Finer-Moore, J.S.,Stroud, R.M.
Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer.
Proc.Natl.Acad.Sci.USA, 111:3865-3870, 2014

PubMed Abstract: 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 14α-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.

PubMed: 24613931
DOI: 10.1073/pnas.1324245111

実験手法

X-RAY DIFFRACTION (2.19 Å)