PMID- 16563352
OWN - NLM
STAT- MEDLINE
DCOM- 20060524
LR  - 20131121
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 343
IP  - 3
DP  - 2006 May 12
TI  - Binding of bufuralol, dextromethorphan, and 3,4-methylenedioxymethylamphetamine 
      to wild-type and F120A mutant cytochrome P450 2D6 studied by resonance Raman 
      spectroscopy.
PG  - 772-9
AB  - 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.
FAU - Bonifacio, Alois
AU  - Bonifacio A
AD  - Laser Centre/Analytical Chemistry and Applied Spectroscopy, Vrije Universiteit 
      Amsterdam, The Netherlands.
FAU - Keizers, Peter H J
AU  - Keizers PH
FAU - Commandeur, Jan N M
AU  - Commandeur JN
FAU - Vermeulen, Nico P E
AU  - Vermeulen NP
FAU - Robert, Bruno
AU  - Robert B
FAU - Gooijer, Cees
AU  - Gooijer C
FAU - van der Zwan, Gert
AU  - van der Zwan G
LA  - eng
PT  - Journal Article
DEP - 20060320
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Ethanolamines)
RN  - 42VZT0U6YR (Heme)
RN  - 7355X3ROTS (Dextromethorphan)
RN  - 891H89GFT4 (bufuralol)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2D6)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Amino Acid Substitution
MH  - Binding Sites
MH  - Cytochrome P-450 CYP2D6/*chemistry/genetics
MH  - Dextromethorphan/*chemistry/metabolism
MH  - Ethanolamines/*chemistry/metabolism
MH  - Heme/chemistry
MH  - Humans
MH  - Mutation
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*chemistry/metabolism
MH  - Spectrum Analysis, Raman
EDAT- 2006/03/28 09:00
MHDA- 2006/05/25 09:00
CRDT- 2006/03/28 09:00
PHST- 2006/03/06 00:00 [received]
PHST- 2006/03/07 00:00 [accepted]
PHST- 2006/03/28 09:00 [pubmed]
PHST- 2006/05/25 09:00 [medline]
PHST- 2006/03/28 09:00 [entrez]
AID - S0006-291X(06)00550-X [pii]
AID - 10.1016/j.bbrc.2006.03.027 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2006 May 12;343(3):772-9. doi: 
      10.1016/j.bbrc.2006.03.027. Epub 2006 Mar 20.