7WY3

Structure of the Oxomolybdenum Mesoporphyrin IX-Reconstituted CYP102A1 F87V Mutant Haem Domain with N-(5-Cyclohexyl)valeroyl-L-Phenylalanine in complex with Styrene

Summary for 7WY3

• Entry DOI: 10.2210/pdb7wy3/pdb
• Descriptor: Bifunctional cytochrome P450/NADPH--P450 reductase, Oxomolybdenum Mesoporphyrin IX, (2~{S})-2-(5-cyclohexylpentanoylamino)-3-phenyl-propanoic acid, ... (7 entities in total)
• Functional Keywords: monooxygenase, oxidoreductase
• Biological source: Priestia megaterium
• Total number of polymer chains: 2
• Total formula weight: 108089.88

Authors

Suzuki, K.,Stanfield, J.K.,Shisaka, Y.,Omura, K.,Kasai, C.,Sugimoto, H.,Shoji, O. (deposition date: 2022-02-15, release date: 2023-01-04, Last modification date: 2023-11-29)

Primary citation

Suzuki, K.,Stanfield, J.K.,Omura, K.,Shisaka, Y.,Ariyasu, S.,Kasai, C.,Aiba, Y.,Sugimoto, H.,Shoji, O.
A Compound I Mimic Reveals the Transient Active Species of a Cytochrome P450 Enzyme: Insight into the Stereoselectivity of P450-Catalysed Oxidations.
Angew.Chem.Int.Ed.Engl., 62:e202215706-e202215706, 2023

PubMed Abstract: Catching the structure of cytochrome P450 enzymes in flagrante is crucial for the development of P450 biocatalysts, as most structures collected are found trapped in a precatalytic conformation. At the heart of P450 catalysis lies Cpd I, a short-lived, highly reactive intermediate, whose recalcitrant nature has thwarted most attempts at capturing catalytically relevant poses of P450s. We report the crystal structure of P450BM3 mimicking the state in the precise moment preceding epoxidation, which is in perfect agreement with the experimentally observed stereoselectivity. This structure was attained by incorporation of the stable Cpd I mimic oxomolybdenum mesoporphyrin IX into P450BM3 in the presence of styrene. The orientation of styrene to the Mo-oxo species in the crystal structures sheds light onto the dynamics involved in the rotation of styrene to present its vinyl group to Cpd I. This method serves as a powerful tool for predicting and modelling the stereoselectivity of P450 reactions.

PubMed: 36519803
DOI: 10.1002/anie.202215706

Experimental method

X-RAY DIFFRACTION (1.6 Å)