7WDH

Crystal structure of the P450 BM3 heme domain mutant F87A in complex with N-imidazolyl-hexanoyl-L-phenylalanine, phenol and hydroxylamine

Summary for 7WDH

• Entry DOI: 10.2210/pdb7wdh/pdb
• Descriptor: Bifunctional cytochrome P450/NADPH--P450 reductase, PROTOPORPHYRIN IX CONTAINING FE, HYDROXYAMINE, ... (6 entities in total)
• Functional Keywords: dual-functional small molecule, p450 heme domain, complex, oxidoreductase
• Biological source: Priestia megaterium
• Total number of polymer chains: 2
• Total formula weight: 109980.90

Authors

Jiang, Y.,Dong, S.,Feng, Y.,Cong, Z. (deposition date: 2021-12-21, release date: 2022-12-28, Last modification date: 2023-11-29)

Primary citation

Wang, X.,Lin, X.,Jiang, Y.,Qin, X.,Ma, N.,Yao, F.,Dong, S.,Liu, C.,Feng, Y.,Jin, L.,Xian, M.,Cong, Z.
Engineering Cytochrome P450BM3 Enzymes for Direct Nitration of Unsaturated Hydrocarbons.
Angew.Chem.Int.Ed.Engl., 62:e202217678-e202217678, 2023

PubMed Abstract: Applications of the peroxidase activity of cytochrome P450 enzymes in synthetic chemistry remain largely unexplored. We present herein a protein engineering strategy to increase cytochrome P450BM3 peroxidase activity for the direct nitration of aromatic compounds and terminal aryl-substituted olefins in the presence of a dual-functional small molecule (DFSM). Site-directed mutations of key active-site residues allowed the efficient regulation of steric effects to limit substrate access and, thus, a significant decrease in monooxygenation activity and increase in peroxidase activity. Nitration of several phenol and aniline compounds also yielded ortho- and para-nitration products with moderate-to-high total turnover numbers. Besides direct aromatic nitration by P450 variants using nitrite as a nitrating agent, we also demonstrated the use of the DFSM-facilitated P450 peroxidase system for the nitration of the vinyl group of styrene and its derivatives.

PubMed: 36660956
DOI: 10.1002/anie.202217678

Experimental method

X-RAY DIFFRACTION (1.68 Å)