9CJG

P450-G9 from Actinokineospora terrae, a non-canonical, serine-ligated cytochrome P450 in the ligand-free, closed conformation

Summary for 9CJG

• Entry DOI: 10.2210/pdb9cjg/pdb
• Descriptor: Cytochrome P450-G9, PROTOPORPHYRIN IX CONTAINING FE, FORMIC ACID, ... (5 entities in total)
• Functional Keywords: p450, cytochrome, serine, p411, oxidoreductase
• Biological source: Actinokineospora terrae
• Total number of polymer chains: 2
• Total formula weight: 90331.68

Authors

Ireland, K.A.,Davis, K.M. (deposition date: 2024-07-06, release date: 2025-03-12, Last modification date: 2026-08-12)

Primary citation

Nguy, A.K.L.,Ireland, K.A.,Kayrouz, C.M.,Caceres, J.C.,Huang, J.Z.,Ying, V.Y.,Quaye, J.A.,Greene, B.L.,Davis, K.M.,Seyedsayamdost, M.R.
Discovery of noncanonical cytochrome P450 enzymes in nature.
Nat.Chem.Biol., 2026

PubMed Abstract: Cytochrome P450s (CYPs) constitute a superfamily of thiolate-ligated heme metalloenzymes principally responsible for the hydroxylation of unactivated C-H bonds. The proximal cysteine is an obligatory and universally conserved residue for the CYP enzyme class. Herein, we challenge this paradigm by systematically identifying noncanonical CYPs (ncCYPs) that do not harbor a proximal cysteine ligand. Our bioinformatic search revealed 20 distinct ncCYP families encoded in diverse microbial genomes with alternative residues at this position. We characterize a native serine-ligated CYP with a high-spin ferric resting state that catalyzes azide reduction and nitrene insertion reactions. Its crystal structure clearly shows a typical CYP fold and a serine alkoxide as a proximal heme ligand. In addition, we report the discovery and characterization of the first native selenocysteine-ligated CYP in nature. Our findings expand the CYP metalloenzyme family and provide opportunities for future enzymatic and biocatalytic discoveries.

PubMed: 42332020
DOI: 10.1038/s41589-026-02235-9

Experimental method

X-RAY DIFFRACTION (1.85 Å)