ArticleJournal of the American Chemical Society2012
Proximal ligand electron donation and reactivity of the cytochrome P450 ferric-peroxo anion.
Article in Journal of the American Chemical Society, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 54 citations in OpenAlex.
- Modulation of heme peroxo nucleophilicities with axial ligands reveal key insights into the mechanistic landscape of nitric oxide synthase.Chemical science · 2025Article
- CYP3A-Mediated Carbon-Carbon Bond Cleavages in Drug Metabolism.Biomolecules · 2024Review
- Updates on Mechanisms of Cytochrome P450 Catalysis of Complex Steroid Oxidations.International journal of molecular sciences · 2024Review
- Noncanonical Amino Acids in Biocatalysis.Chemical reviews · 2024Review
- CYP3A Mediates an Unusual C(spAngewandte Chemie (International ed. in English) · 2024Article
- Oxygen-18 Labeling Reveals a Mixed Fe-O Mechanism in the Last Step of Cytochrome P450 51 Sterol 14α-Demethylation.Angewandte Chemie (International ed. in English) · 2024Article
- Oxygen-18 Labeling Defines a Ferric Peroxide (Compound 0) Mechanism in the Oxidative Deformylation of Aldehydes by Cytochrome P450 2B4.ACS catalysis · 2024Article
- Electron Transfer Mechanism at the Interface of Multi-Heme Cytochromes and Metal Oxide.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Theoretical Study of Hydroxylation of α- and β-Pinene by a Cytochrome P450 Monooxygenase Model.International journal of molecular sciences · 2023Article
- Melatonin Activation by Cytochrome P450 Isozymes: How Does CYP1A2 Compare to CYP1A1?International journal of molecular sciences · 2023Article
- Engineering enzyme activity using an expanded amino acid alphabet.Protein engineering, design & selection : PEDS · 2023Article
- End-On Copper(I) Superoxo and Cu(II) Peroxo and Hydroperoxo Complexes Generated by Cryoreduction/Annealing and Characterized by EPR/ENDOR Spectroscopy.Journal of the American Chemical Society · 2022Article
- A Noncanonical Tryptophan Analogue Reveals an Active Site Hydrogen Bond Controlling Ferryl Reactivity in a Heme Peroxidase.JACS Au · 2021Article
- Rewiring the "Push-Pull" Catalytic Machinery of a Heme Enzyme Using an Expanded Genetic Code.ACS catalysis · 2020Article
- A Promiscuous Cytochrome P450 Hydroxylates Aliphatic and Aromatic C-H Bonds of Aromatic 2,5-Diketopiperazines.Chembiochem : a European journal of chemical biology · 2019Article
- Formation and Cleavage of C-C Bonds by Enzymatic Oxidation-Reduction Reactions.Chemical reviews · 2018Review
- Potential drug targets in the Mycobacterium tuberculosis cytochrome P450 system.Journal of inorganic biochemistry · 2018Review
- How Do Ring Size and π-Donating Thiolate Ligands Affect Redox-Active, α-Imino-N-heterocycle Ligand Activation?Inorganic chemistry · 2018Article
- Spectroscopic studies of the cytochrome P450 reaction mechanisms.Biochimica et biophysica acta. Proteins and proteomics · 2018Review
- Active Site Structures of CYP11A1 in the Presence of Its Physiological Substrates and Alterations upon Binding of Adrenodoxin.Biochemistry · 2017Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
CYP125 from Mycobacterium tuberculosis catalyzes sequential oxidation of the cholesterol side-chain terminal methyl group to the alcohol, aldehyde, and finally acid. Here, we demonstrate that CYP125 simultaneously catalyzes the formation of five other products, all of which result from deformylation of the sterol side chain. The aldehyde intermediate is shown to be the precursor of both the conventional acid metabolite and the five deformylation products. The acid arises by protonation of the ferric-peroxo anion species and formation of the ferryl-oxene species, also known as Compound I, followed by hydrogen abstraction and oxygen transfer. The deformylation products arise by addition of the same ferric-peroxo anion to the aldehyde intermediate to give a peroxyhemiacetal that leads to C-C bond cleavage. This bifurcation of the catalytic sequence has allowed us to examine the effect of electron donation by the proximal ligand on the properties of the ferric-peroxo anion. Replacement of the cysteine thiolate iron ligand by a selenocysteine results in UV-vis, EPR, and resonance Raman spectral changes indicative of an increased electron donation from the proximal selenolate ligand to the iron. Analysis of the product distribution in the reaction of the selenocysteine substituted enzyme reveals a gain in the formation of the acid (Compound I pathway) at the expense of deformylation products. These observations are consistent with an increase in the pK(a) of the ferric-peroxo anion, which favors its protonation and, therefore, Compound I formation.
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