ArticleJournal of the American Chemical Society2011
Does compound I vary significantly between isoforms of cytochrome P450?
Article in Journal of the American Chemical Society, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
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- Mechanism of the Oxidative Ring-Closure Reaction during Gliotoxin Biosynthesis by Cytochrome P450 GliF.International journal of molecular sciences · 2024Article
- Melatonin Activation by Human Cytochrome P450 Enzymes: A Comparison between Different Isozymes.Molecules (Basel, Switzerland) · 2023Article
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- Investigating the Active Oxidants Involved in Cytochrome P450 Catalyzed Sulfoxidation Reactions.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Spin state dependent peroxidase activity of heme bound amyloid β peptides relevant to Alzheimer's disease.Chemical science · 2022Article
- Mechanism of Melatonin Metabolism by CYP1A1: What Determines the Bifurcation Pathways of Hydroxylation versus Deformylation?The journal of physical chemistry. B · 2022Article
- Reliably assessing the electronic structure of cytochrome P450 on today's classical computers and tomorrow's quantum computers.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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- Tris(Butadiene) Compounds versus Butadiene Oligomerization in Second-Row Transition Metal Chemistry: Effects of Increased Ligand Fields.Molecules (Basel, Switzerland) · 2021Article
- CYP154C5 Regioselectivity in Steroid Hydroxylation Explored by Substrate Modifications and Protein Engineering*.Chembiochem : a European journal of chemical biology · 2021Article
- Lignin Biodegradation by a Cytochrome P450 Enzyme: A Computational Study into Syringol Activation by GcoA.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
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- In Silico Predictions of Endocrine Disruptors Properties.Endocrinology · 2019Review
- Computational explanation for bioactivation mechanism of targeted anticancer agents mediated by cytochrome P450s: A case of Erlotinib.PloS one · 2017Article
- Binuclear rhenium carbonyl nitrosyls related to dicobalt octacarbonyl and their decarbonylation products.Journal of molecular modeling · 2016Article
- A comprehensive test set of epoxidation rate constants for iron(iv)-oxo porphyrin cation radical complexes.Chemical science · 2015Article
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4 authors.
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Abstract
The cytochrome P450 (CYP) enzymes are important in many areas, including pharmaceutical development. Subtle changes in the electronic structure of the active species, Compound I, have been postulated previously to account partly for the experimentally observed differences in reactivity between isoforms. Current predictive models of CYP metabolism typically assume an identical Compound I in all isoforms. Here we present a method to calculate the electronic structure and to estimate the Fe-O bond enthalpy of Compound I, and apply it to several human and bacterial CYP isoforms. Conformational flexibility is accounted for by sampling large numbers of structures from molecular dynamics simulations, which are subsequently optimized with density functional theory (B3LYP) based quantum mechanics/molecular mechanics. The observed differences in Compound I between human isoforms are small: They are generally smaller than the spread of values obtained for the same isoform starting from different initial structures. Hence, it is unlikely that the variation in activity between human isoforms is due to differences in the electronic structure of Compound I. A larger difference in electronic structure is observed between the human isoforms and P450(cam) and may be explained by the slightly different hydrogen-bonding environment surrounding the cysteinyl sulfur. The presence of substrate in the active site of all isoforms studied appears to cause a slight decrease in the Fe-O bond enthalpy, apparently due to displacement of water out of the active site, suggesting that Compound I is less stable in the presence of substrate.
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