ArticleArchives of biochemistry and biophysics2011
The kinetic mechanism for cytochrome P450 metabolism of type II binding compounds: evidence supporting direct reduction.
Article in Archives of biochemistry and biophysics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Enzyme engineering of cytochrome P450 RosC provides mechanistic insights into factors controlling iterative oxidation.Applied microbiology and biotechnology · 2025Article
- Evaluation of Larger Side-Group Functionalities and the Side/End-Group Interplay in Ritonavir-Like Inhibitors of CYP3A4.Chemical biology & drug design · 2025Article
- Drug metabolism of ciprofloxacin, ivacaftor, and raloxifene by Pseudomonas aeruginosa cytochrome P450 CYP107S1.The Journal of biological chemistry · 2024Article
- Heme Spin Distribution in the Substrate-Free and Inhibited Novel CYP116B5hd: A Multifrequency Hyperfine Sublevel Correlation (HYSCORE) Study.Molecules (Basel, Switzerland) · 2024Article
- Enzyme Kinetics, Pharmacokinetics, and Inhibition of Aldehyde Oxidase.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Drug modulation of water-heme interactions in low-spin P450 complexes of CYP2C9d and CYP125A1.Biochemistry · 2015Article
- Use of chemical auxiliaries to control p450 enzymes for predictable oxidations at unactivated C-h bonds of substrates.Advances in experimental medicine and biology · 2015Review
- Current Approaches for Investigating and Predicting Cytochrome P450 3A4-Ligand Interactions.Advances in experimental medicine and biology · 2015Review
- Controlling substrate specificity and product regio- and stereo-selectivities of P450 enzymes without mutagenesis.Bioorganic & medicinal chemistry · 2014Review
- A structural snapshot of CYP2B4 in complex with paroxetine provides insights into ligand binding and clusters of conformational states.The Journal of pharmacology and experimental therapeutics · 2013Article
- Predicting intrinsic clearance for drugs and drug candidates metabolized by aldehyde oxidase.Molecular pharmaceutics · 2013Article
- Measurement of electron transfer through cytochrome P450 protein on nanopillars and the effect of bound substrates.Journal of the American Chemical Society · 2013Article
- Binding of a cyano- and fluoro-containing drug bicalutamide to cytochrome P450 46A1: unusual features and spectral response.The Journal of biological chemistry · 2013Article
- 1,2,3-Triazole-heme interactions in cytochrome P450: functionally competent triazole-water-heme complexes.Biochemistry · 2012Article
- Crystal structure of human cytochrome P450 2D6 with prinomastat bound.The Journal of biological chemistry · 2012Article
- Stereospecific metabolism of itraconazole by CYP3A4: dioxolane ring scission of azole antifungals.Drug metabolism and disposition: the biological fate of chemicals · 2012Article
- Comparative study of the affinity and metabolism of type I and type II binding quinoline carboxamide analogues by cytochrome P450 3A4.Journal of medicinal chemistry · 2012Article
- Small molecule quantification by liquid chromatography-mass spectrometry for metabolites of drugs and drug candidates.Drug metabolism and disposition: the biological fate of chemicals · 2011Article
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Authors and funding
7 authors.
Funding
Abstract
The metabolic stability of a drug is an important property that should be optimized during drug design and development. Nitrogen incorporation is hypothesized to increase the stability by coordination of nitrogen to the heme iron of cytochrome P450, a binding mode that is referred to as type II binding. However, we noticed that the type II binding compound 1 has less metabolic stability at sub-saturating conditions than a closely related type I binding compound 3. Three kinetic models will be presented for type II binder metabolism; (1) Dead-end type II binding, (2) a rapid equilibrium between type I and II binding modes before reduction, and (3) a direct reduction of the type II coordinated heme. Data will be presented on reduction rates of iron, the off rates of substrate (using surface plasmon resonance) and the catalytic rate constants. These data argue against the dead-end, and rapid equilibrium models, leaving the direct reduction kinetic mechanism for metabolism of the type II binding compound 1.
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