Non-Canonical Cytochrome P450 Enzymes in Nature
Nguy, A. K. L.; Ireland, K. A.; Kayrouz, C. M.; Caceres, J. C.; Greene, B. L.; Davis, K. M.; Seyedsayamdost, M. R.
Show abstract
Cytochrome P450s (CYPs) are a superfamily of thiolate-ligated heme metalloenzymes principally responsible for the hydroxylation of unactivated C-H bonds. The lower-axial cysteine is an obligatory and universally conserved residue for the CYP enzyme class. Herein, we challenge this paradigm by systematically identifying non-canonical CYPs (ncCYPs) that do not harbor a cysteine ligand. Our bioinformatic search reveals 20 distinct ncCYP families with diverse ligands encoded in microbial genomes. We characterize a native serine-ligated CYP with a high-spin ferric resting state. Its crystal structure clearly shows a typical CYP fold and a serine alkoxide as a lower axial heme ligand. In addition, we report the discovery and characterization of the first native selenocysteine-ligated CYP in nature. Our findings radically expand the CYP metalloenzyme family.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Menaquinone-specific oxidation by M. tuberculosis cytochrome bd is redox regulated by the Q-loop disulfide bond 96%
- A natural fusion of flavodiiron, rubredoxin, and NADH:rubredoxin oxidoreductase domains is the highly efficient water-forming oxidase of T. vaginalis 95%
- Novel exported bifunctional fusion enzymes with chorismate mutase and cyclohexadienyl dehydratase activity: shikimate pathway enzymes teamed up in no man's land 94%
Similar papers in this journal
- Structure and Mechanism of Avermitilol Synthase, a Sesquiterpene Cyclase that Generates a Highly Strained 6-6-3 Tricyclic Alcohol 95%
- Mechanism Underlying Anti-Markovnikov Addition in the Reaction of Pentalenene Synthase 94%
- The Crystal Structures of Bacillithiol Disulfide Reductase YpdA Reveal Structural and Functional Insight into a New Type of FAD-Containing NADPH-Dependent Oxidoreductases 94%
Similar papers in this journal
- Structures of two LarA-like nickel-pincer nucleotide cofactor-utilizing enzymes with a single catalytic histidine residue 94%
- The role of evolutionarily metastable oligomeric states in the optimization of catalytic activity 94%
- A suicidal and extensively disordered luciferase with a bright luminescence 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.