Molecular modelling of cytochrome P4502D6 (CYP2D6) based on an alignment with CYP102: structural studies on specific CYP2D6 substrate metabolism.
Xenobiotica
; 27(4): 319-39, 1997 Apr.
Article
em En
| MEDLINE
| ID: mdl-9149373
ABSTRACT
1. A molecular model of CYP2D6 has been constructed from the bacterial form CYP102 via a homology alignment between the CYP2D subfamily and CYP102 protein sequences. 2. A number of typical CYP2D6 substrates are shown to fit the putative active site of the enzyme, as can the specific inhibitor quinidine. 3. Some of the allelic variants in CYP2D6, which give rise to genetic polymorphisms in 2D6-mediated metabolism, can be rationalized in terms of their position within the active site region. 4. The results of site-directed mutagenesis experiments are consistent with the CYP2D6 model generated from the CYP102 crystal structure. 5. The possibility of an alternative orientation within the active site may explain the CYP2D6-mediated metabolism of relatively large-sized substrates.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
/
Citocromo P-450 CYP2D6
/
Sistema Enzimático do Citocromo P-450
/
Oxigenases de Função Mista
/
Isoenzimas
Idioma:
En
Revista:
Xenobiotica
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Reino Unido