How Similar Are P450s and What Can Their Differences Teach Us?

Cytochromes P450 form a very large superfamily of proteins which metabolize substrates from steroids to fatty acids to drugs and are found in organisms from protists to mammals. P450s all appear to take on a similar structural fold, yet frequently having less than 20% sequence identity and having va...

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Bibliographic Details
Published in:Archives of Biochemistry and Biophysics 1999-09, Vol.369 (1), p.24-29
Main Authors: Graham, Sandra E., Peterson, Julian A.
Format: Article
Language:English
Subjects:
Binding Sites
chemical structure
cytochrome P-450
Cytochrome P-450 Enzyme System - chemistry
Evolution, Molecular
Models, Molecular
P450
Protein Folding
protein secondary structure
protein structure
Protein Structure, Secondary
Space life sciences
structural analysis
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Summary:Cytochromes P450 form a very large superfamily of proteins which metabolize substrates from steroids to fatty acids to drugs and are found in organisms from protists to mammals. P450s all appear to take on a similar structural fold, yet frequently having less than 20% sequence identity and having vastly different substrates. Within the structural fold there appears to be a highly conserved core, as determined from the comparison of the structures of the six crystallized, soluble P450s. There are also variable regions which by and large appear to be associated with substrate recognition, substrate binding, and redox partner binding. Molecular dynamics simulations of motion in P450cam and P450BM-3 indicate that substrate binding and product release require substantial motion around the “substrate access channel.” Additionally, at the 11th International Conference on Cytochrome P450 Biochemistry, Biophysics, and Molecular Biology and briefly here, the first structure of a microsomal eukaryotic P450 will be presented and compared to the already determined structures by Drs. Johnson and McRee. Finally, with a better understanding of the structure/function relationship of P450s, one will be better able to modify P450s to metabolize the substrates of choice or produce needed valuable chemicals.
ISSN:0003-9861
1096-0384
DOI:10.1006/abbi.1999.1350