Midazolam oxidation by cytochrome P450 3A4 and active-site mutants: An evaluation of multiple binding sites and of the metabolic pathway that leads to enzyme inactivation

Molecular Pharmacology

Volumn 61, Issue 3, 2002, Pages 495-506

  Khan, Kishore K ^a   You, Qun He ^a   Domanski, Tammy L ^a   Halpert, James R ^a  

^a University of Texas Medical Branch School of Medicine   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; AMINO ACID; CYTOCHROME P450 3A4; ISOLEUCINE; LEUCINE; MIDAZOLAM; PHENYLALANINE; SERINE; THREONINE; TYROSINE;

AMINO ACID SUBSTITUTION; ARTICLE; BINDING SITE; CONCENTRATION RESPONSE; DRUG HYDROXYLATION; DRUG METABOLISM; DRUG OXIDATION; ENZYME INACTIVATION; KINETICS; MOLECULAR RECOGNITION; NONHUMAN; PRIORITY JOURNAL; STEREOCHEMISTRY;

AMINO ACID SUBSTITUTION; ANESTHETICS, INTRAVENOUS; ANIMALS; BINDING SITES; CYTOCHROME P-450 ENZYME SYSTEM; ENZYME INHIBITORS; MIDAZOLAM; MIXED FUNCTION OXYGENASES; MODELS, MOLECULAR; MUTATION; OXIDATION-REDUCTION; RATS; STATISTICS;

EID: 0036178095     PISSN: 0026895X     EISSN: None     Source Type: Journal    
DOI: 10.1124/mol.61.3.495     Document Type: Article

References (40)

1. Crystal structures of ligand complexes of P450eryF exhibiting homotropic cooperativity
2. Analysis of mammalian cytochrome P450 structure and function using site-directed mutagenesis
3. Dual role of human cytochrome P450 3A4 residue Phe-304 in substrate specificity and cooperativity
4. Phenylalanine and tryptophan scanning mutagenesis of CYP3A4 substrate recognition site residue and the effect on substrate oxidation and cooperativity
5. Analysis of four residues within substrate recognition site 4 of human cytochrome P450 3A4: Role in steroid hydroxylase activity and alpha-naphthoflavone stimulation
6. Identification and functional characterization of eight CYP3A4 protein variants
7. Systematic screening for pharmacokinetic interactions during drug development
8. Inhibition and kinetics of cytochrome P4503A activity in microsomes from rat, human, and cDNA-expressed human cytochrome P450
9. Regioselective biotransformation of MDZ by members of the human cytochrome P450 3A (CYP3A) subfamily
10. Substrate recognition sites in cytochrome P450 family 2 (CYP2) proteins inferred from comparative analyses of amino acid and coding nucleotide sequences
11. Human cytochrome P450 enzymes
12. Alanine-scanning mutagenesis of a putative substrate recognition site in human cytochrome P450 3A4. Role of residues 210 and 211 in flavonoid activation and substrate specificity
13. Analysis of human cytochrome P450 3A4 cooperativity: Construction and characterization of a site-directed mutant that displays hyperbolic steroid hydroxylation kinetics
14. Structure and function of cytochromes P450: A comparative analysis of three crystal structures
15. Identification of three key residues in substrate recognition site 5 of human cytochrome P450 3A4 by cassette and site-directed mutagenesis
16. Elucidation of distinct ligand binding sites for cytochrome P450 3A4
17. Structure-function analysis of human cytochrome P450 3A4 using 7-alkoxycoumarins as active-site probes
18. Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein
19. CO binding kinetics of human cytochrome P450 3A4. Specific interaction of substrates with kinetically distinguishable conformers
20. Evaluation of atypical cytochrome P450 kinetics with two-substrate models: Evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites
21. Oxidation of midazolam and triazolam by human liver cytochrome P45OIIIA4
22. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression
23. Specific dehydrogenation of 3-methylindole and epoxidation of naphthalene by recombinant human CYP2F1 expressed in lymphoblastoid cells
24. Human cytochrome P450 3A (CYP3A) mediated midazolam metabolism: The effect of assay conditions and regioselective stimulation by alpha-naphthoflavone, terfenadine and testosterone
25. Midazolam: A review of therapeutic uses and toxicity
26. Midazolam and triazolam biotransformation in mouse and human liver microsomes: Relative contribution of CYP3A and CYP2C isoforms
27. Evidence supporting mechanism-based inactivation of CYP3A by midazolam
28. The importance of SRS-1 residues in catalytic specificity of human cytochrome P450 3A4
29. Covalent alteration of the CYP3A4 active site: Evidence for multiple substrate binding domains
30. Modulation of rabbit and human hepatic cytochrome P-45O-catatyzed steroid hydroxylations by α-naphthoflavone
31. A kinetic model for the metabolic interaction of two substrates at the active site of cytochrome P450 3A4
32. Activation of CYP3A4: Evidence for the simultaneous binding of two substrates in a cytochrome P450 active site
33. Molecular modeling of cytochrome P450 3A4
34. Use of the steroid derivative RPR 106541 in combination with site-directed mutagenesis for enhanced cytochrome P-450 3A4 structure/function analysis
35. In vitro and in vivo drug interactions involving human CYP3A4
36. Cooperativity in oxidations catalyzed by cytochrome P450 3A4
37. Structure-function relationships of human liver cytochromes P450 3A: Aflatoxin B1 metabolism as a probe
38. Human cytochrome P-450 3A4 in vitro drug-drug interaction patterns are substrate-dependent
39. Mammalian microsomal cytochrome P450 monooxygenase: Structural adaptations for membrane binding and functional diversity
40. 1 oxidation