4LXJ

Saccharomyces cerevisiae lanosterol 14-alpha demethylase with lanosterol bound

Summary for 4LXJ

• Entry DOI: 10.2210/pdb4lxj/pdb
• Descriptor: Lanosterol 14-alpha demethylase, PROTOPORPHYRIN IX CONTAINING FE, LANOSTEROL, ... (5 entities in total)
• Functional Keywords: cytochrome p450, oxidoreductase
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Cellular location: Membrane; Single-pass membrane protein: P10614
• Total number of polymer chains: 1
• Total formula weight: 62545.97

Authors

Monk, B.C.,Tomasiak, T.M.,Keniya, M.V.,Huschmann, F.U.,Tyndall, J.D.A.,O'Connell III, J.D.,Cannon, R.D.,McDonald, J.,Rodriguez, A.,Finer-Moore, J.,Stroud, R.M. (deposition date: 2013-07-29, release date: 2014-01-29, Last modification date: 2023-09-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)