Tags

Type your tag names separated by a space and hit enter

Binding of bufuralol, dextromethorphan, and 3,4-methylenedioxymethylamphetamine to wild-type and F120A mutant cytochrome P450 2D6 studied by resonance Raman spectroscopy.
Biochem Biophys Res Commun. 2006 May 12; 343(3):772-9.BB

Abstract

Cytochrome P450 2D6 (CYP2D6) is one of the most important drug-metabolizing enzymes in humans. Resonance Raman data, reported for the first time for CYP2D6, show that the CYP2D6 heme is found to be in a six-coordinated low-spin state in the absence of substrates, and it is perturbed to different extents by bufuralol, dextromethorphan, and 3,4-methylenedioxymethylamphetamine (MDMA). Dextromethorphan and MDMA induce in CYP2D6 a significant amount of five-coordinated high-spin heme species and reduce the polarity of its heme-pocket, whereas bufuralol does not. Spectra of the F120A mutant CYP2D6 suggest that Phe120 is involved in substrate-binding of dextromethorphan and MDMA, being responsible for the spectral differences observed between these two compounds and bufuralol. These differences could be explained postulating a different substrate mobility for each compound in the CYP2D6 active site, consistently with the role previously suggested for Phe120 in binding dextromethorphan and MDMA.

Authors+Show Affiliations

Laser Centre/Analytical Chemistry and Applied Spectroscopy, Vrije Universiteit Amsterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16563352

Citation

Bonifacio, Alois, et al. "Binding of Bufuralol, Dextromethorphan, and 3,4-methylenedioxymethylamphetamine to Wild-type and F120A Mutant Cytochrome P450 2D6 Studied By Resonance Raman Spectroscopy." Biochemical and Biophysical Research Communications, vol. 343, no. 3, 2006, pp. 772-9.
Bonifacio A, Keizers PH, Commandeur JN, et al. Binding of bufuralol, dextromethorphan, and 3,4-methylenedioxymethylamphetamine to wild-type and F120A mutant cytochrome P450 2D6 studied by resonance Raman spectroscopy. Biochem Biophys Res Commun. 2006;343(3):772-9.
Bonifacio, A., Keizers, P. H., Commandeur, J. N., Vermeulen, N. P., Robert, B., Gooijer, C., & van der Zwan, G. (2006). Binding of bufuralol, dextromethorphan, and 3,4-methylenedioxymethylamphetamine to wild-type and F120A mutant cytochrome P450 2D6 studied by resonance Raman spectroscopy. Biochemical and Biophysical Research Communications, 343(3), 772-9.
Bonifacio A, et al. Binding of Bufuralol, Dextromethorphan, and 3,4-methylenedioxymethylamphetamine to Wild-type and F120A Mutant Cytochrome P450 2D6 Studied By Resonance Raman Spectroscopy. Biochem Biophys Res Commun. 2006 May 12;343(3):772-9. PubMed PMID: 16563352.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Binding of bufuralol, dextromethorphan, and 3,4-methylenedioxymethylamphetamine to wild-type and F120A mutant cytochrome P450 2D6 studied by resonance Raman spectroscopy. AU - Bonifacio,Alois, AU - Keizers,Peter H J, AU - Commandeur,Jan N M, AU - Vermeulen,Nico P E, AU - Robert,Bruno, AU - Gooijer,Cees, AU - van der Zwan,Gert, Y1 - 2006/03/20/ PY - 2006/03/06/received PY - 2006/03/07/accepted PY - 2006/3/28/pubmed PY - 2006/5/25/medline PY - 2006/3/28/entrez SP - 772 EP - 9 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 343 IS - 3 N2 - Cytochrome P450 2D6 (CYP2D6) is one of the most important drug-metabolizing enzymes in humans. Resonance Raman data, reported for the first time for CYP2D6, show that the CYP2D6 heme is found to be in a six-coordinated low-spin state in the absence of substrates, and it is perturbed to different extents by bufuralol, dextromethorphan, and 3,4-methylenedioxymethylamphetamine (MDMA). Dextromethorphan and MDMA induce in CYP2D6 a significant amount of five-coordinated high-spin heme species and reduce the polarity of its heme-pocket, whereas bufuralol does not. Spectra of the F120A mutant CYP2D6 suggest that Phe120 is involved in substrate-binding of dextromethorphan and MDMA, being responsible for the spectral differences observed between these two compounds and bufuralol. These differences could be explained postulating a different substrate mobility for each compound in the CYP2D6 active site, consistently with the role previously suggested for Phe120 in binding dextromethorphan and MDMA. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/16563352/Binding_of_bufuralol_dextromethorphan_and_34_methylenedioxymethylamphetamine_to_wild_type_and_F120A_mutant_cytochrome_P450_2D6_studied_by_resonance_Raman_spectroscopy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(06)00550-X DB - PRIME DP - Unbound Medicine ER -