Kinetics and thermodynamics of ligand binding by cytochrome P450 3A4
Emre M. Isin,F. Peter Guengerich +1 more
TLDR
A three-step substrate binding model is proposed, based on absorbance and fluorescence stopped-flow kinetic data and equilibrium binding data obtained with bromocriptine, and evaluated using kinetic modeling.About:
This article is published in Journal of Biological Chemistry.The article was published on 2006-04-07 and is currently open access. It has received 140 citations till now. The article focuses on the topics: Cooperativity & Cooperative binding.read more
Citations
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Cytochrome P450 and Chemical Toxicology
TL;DR: Crystal structures of several of the major human P450s are now in hand, and unresolved problems include the characterization of the minor "orphan" P 450s, ligand cooperativity and kinetic complexity of several P450S, the prediction of metabolism, the overall contribution of bioactivation to drug idiosyncratic problems, the extrapolation of animal test results to humans in drug development, and the contribution of genetic variation in human P550s to cancer incidence.
Journal ArticleDOI
Nanodiscs in Membrane Biochemistry and Biophysics
TL;DR: This review attempted to combine a comprehensive list of various applications of nanodisc technology with systematic analysis of the most attractive features of this system and advantages provided by nanodISCs for structural and mechanistic studies of membrane proteins.
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LacZ β-galactosidase: structure and function of an enzyme of historical and molecular biological importance.
TL;DR: The structure, function, and catalytic mechanism of lacZ β‐galactosidase, which played a central role in Jacob and Monod's development of the operon model for the regulation of gene expression, is reviewed.
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Structure and mechanism of the complex between cytochrome P4503A4 and ritonavir
TL;DR: The results show that ritonavir is a type II ligand that perfectly fits into the CYP3A4 active site cavity and irreversibly binds to the heme iron via the thiazole nitrogen, which decreases the redox potential of the protein and precludes its reduction with theredox partner, cytochrome P450 reductase.
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Mechanisms of cytochrome P450 substrate oxidation: MiniReview.
TL;DR: A general chemical mechanism can be used to rationalize most of the oxidations and involves a perfenyl intermediate and odd‐electron chemistry, i.e. abstraction of a hydrogen atom or electron followed by oxygen rebound and sometimes rearrangement.
References
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The Carbon Monoxide-binding Pigment of Liver Microsomes I. EVIDENCE FOR ITS HEMOPROTEIN NATURE
Tsuneo Omura,Ryo Sato +1 more
TL;DR: The present paper gives a detailed account of the investigations on rabbit liver microsomes and crude microsomal digests, which have led to postulate the hemoprotein nature of the pigment.
Journal Article
Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians.
TL;DR: The results presented in this study provide useful information for the study of drug biotransformation in humans and for the basis of drug toxicities, carcinogenesis and teratogenesis.
Book
Structure and Mechanism in Protein Science
TL;DR: The three-dimensional structure of proteins chemical catalysis the basic equations of enzyme kinetics measurement and magnitude of enzymatic rate constants the pH dependence of enzyme catalysis practical kinetics detection of intermediaries in reactions by kinetics stereochemistry of enzymes reactions active-site-directed and enzyme-activated irreversible inhibitors - affinity labels and suicide inhibitors conformational change, allosteric regulation, motors and work forces between molecules, and enzymesubstrate binding energies enzyme-substrate complementarity and the use of binding energy in catalysis specificity and editing mechanisms recombinant DNA technology case studies of enzyme
Book
Cytochrome P-450: Structure, Mechanism, and Biochemistry
Ortiz de Montellano,R Paul +1 more
TL;DR: The Cytochrome P450 and the Metabolism and Bioactivation of Arachidonic Acid and Eicosanoids in Plants and the Diversity and Importance of Microbial Cytochromes P450 are studied.
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Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity.
TL;DR: P450s also catalyze less generally discussed reactions including reduction, desaturation, ester cleavage, ring expansion, ring formation, aldehyde scission, dehydration, ipso attack, coupling reactions, rearrangement of fatty acid and prostaglandin hydroperoxides, and phospholipase activity.