Homology modelling of CYP3A4 from the CYP2C5 crystallographic template: analysis of typical CYP3A4 substrate interactions.
Xenobiotica
; 34(6): 549-69, 2004 Jun.
Article
in En
| MEDLINE
| ID: mdl-15277015
ABSTRACT
1. The results of homology modelling of cytochrome P4503A4 (CYP3A4), which is a human enzyme of major importance for the Phase 1 metabolism of drug substrates, from the CYP2C5 crystal structure is reported. 2. The overall homology between the two protein sequences was generally good (46%) with 24% of amino acid residues being identical and a 22% similarity between matched pairs in the CYP3A4 and CYP2C5 aligned sequences, thus indicating that CYP2C5 represents a viable template for modelling CYP3A4 by homology. 3. The CYP3A4 model appears to show consistency with the reported findings from the extensive site-directed mutagenesis studies already published. 4. Typical CYP3A4 substrates, such as midazolam, testosterone, nifedipine and verapamil, are shown to fit the putative active site of the enzyme structure in a manner consistent with their known positions of metabolism.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Steroid 21-Hydroxylase
/
Models, Molecular
/
Cytochrome P-450 Enzyme System
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Xenobiotica
Year:
2004
Document type:
Article
Affiliation country:
Reino Unido