7YDC

Crystal structure of the P450 BM3 heme domain mutant F87L/T268V/V78C in complex with N-imidazolyl-pentanoyl-L-phenylalanine and hydroxylamine

Summary for 7YDC

• Entry DOI: 10.2210/pdb7ydc/pdb
• Descriptor: Bifunctional cytochrome P450/NADPH--P450 reductase, PROTOPORPHYRIN IX CONTAINING FE, HYDROXYAMINE, ... (5 entities in total)
• Functional Keywords: p450 bm3 heme domain, oxidoreductase
• Biological source: Priestia megaterium NBRC 15308 = ATCC 14581
• Total number of polymer chains: 2
• Total formula weight: 108985.91

Authors

Dong, S.,Chen, J.,Jiang, Y.,Cong, Z.,Feng, Y. (deposition date: 2022-07-04, release date: 2023-05-24, Last modification date: 2023-11-29)

Primary citation

Chen, J.,Dong, S.,Fang, W.,Jiang, Y.,Chen, Z.,Qin, X.,Wang, C.,Zhou, H.,Jin, L.,Feng, Y.,Wang, B.,Cong, Z.
Regiodivergent and Enantioselective Hydroxylation of C-H bonds by Synergistic Use of Protein Engineering and Exogenous Dual-Functional Small Molecules.
Angew.Chem.Int.Ed.Engl., 62:e202215088-e202215088, 2023

PubMed Abstract: It is a great challenge to optionally access diverse hydroxylation products from a given substrate bearing multiple reaction sites of sp and sp C-H bonds. Herein, we report the highly selective divergent hydroxylation of alkylbenzenes by an engineered P450 peroxygenase driven by a dual-functional small molecule (DFSM). Using combinations of various P450BM3 variants with DFSMs enabled access to more than half of all possible hydroxylated products from each substrate with excellent regioselectivity (up to >99 %), enantioselectivity (up to >99 % ee), and high total turnover numbers (up to 80963). Crystal structure analysis, molecular dynamic simulations, and theoretical calculations revealed that synergistic effects between exogenous DFSMs and the protein environment controlled regio- and enantioselectivity. This work has implications for exogenous-molecule-modulated enzymatic regiodivergent and enantioselective hydroxylation with potential applications in synthetic chemistry.

PubMed: 36417593
DOI: 10.1002/anie.202215088

Experimental method

X-RAY DIFFRACTION (1.609 Å)