Structure and function of cytochromes P450:a comparative analysis of three crystal structures
| Autor: | Sekhar S. Boddupalli, Julian A. Peterson, Charles A. Hasemann, Ravi G. Kurumbail, Johann Deisenhofer |
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| Rok vydání: | 1995 |
| Předmět: |
Models
Molecular Protein Folding Stereochemistry Molecular Sequence Data Sequence alignment Crystal structure Crystallography X-Ray Protein Structure Secondary Protein structure Cytochrome P-450 Enzyme System Structural Biology Computer Graphics Animals Humans Molecule Amino Acid Sequence Molecular Biology Peptide sequence Binding Sites Sequence Homology Amino Acid Chemistry Protein tertiary structure Crystallography Docking (molecular) Protein folding Oxidation-Reduction |
| Zdroj: | Structure. 3:41-62 |
| ISSN: | 0969-2126 |
| DOI: | 10.1016/s0969-2126(01)00134-4 |
| Popis: | Background: Cytochromes P450 catalyze the oxidation of a variety of hydrophobic substrates. Sequence identities between P450 families are generally low (10–30%), and consequently, the structure–function correlations among P450s are not clear. The crystal structures of P450 terp and the hemoprotein domain of P450 BM-3 were recently determined, and are compared here with the previously available structure of P450 cam . Results The topology of all three enzymes is quite similar. The heme-binding core structure is well conserved, except for local differences in the I helices. The greatest variation is observed in the substrate-binding regions. The structural superposition of the proteins permits an improved sequence alignment of other P450s. The charge distribution in the three structures is similarly asymmetric and defines a molecular dipole. Conclusion Based on this comparison we believe that all P450s will be found to possess the same tertiary structure. The ability to precisely predict other P450 substrate-contact residues is limited by the extreme structural heterogeneity in the substrate-recognition regions. The central I-helix structures of P450 terp and P450 BM-3 suggest a role for helix-associated solvent molecules as a source of catalytic protons, distinct from the mechanism for P450 cam . We suggest that the P450 molecular dipole might aid in both redox-partner docking and proton recruitment for catalysis. |
| Databáze: | OpenAIRE |
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