Is there a relationship between the substrate preferences and structural flexibility of cytochromes P450?
In the last decades, the structural flexibility of cytochromes P450 has been extensively studied by spectroscopic and in silico methods. Here, both approaches are reviewed and compared. Comparison of both methods indicates that the individual cytochromes P450 differ significantly in the flexibilities of their substrate-binding active sites. This finding probably accounts for the large number of isoforms of these enzymes (there are fifty-seven known cytochrome P450 genes in the human genome) and their functional versatility. On the other hand, most of the known cytochrome P450s have a set of common structural features, with an overall structure consisting of a relatively flexible domain (the distal side), a more rigid domain (the heme-binding core) and a domain on the proximal side of the hemoprotein with intermediate flexibility. Substrate access and product egress channels of CYP enzymes are also important structural elements as the majority of these channels are located in the flexible distal side; the location, flexibility, and function of these channels are discussed.
Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University, Olomouc, Czech Republic. michal.otyepka@upol.cz
Michal
M
Otyepka
Karel
K
Berka
Pavel
P
Anzenbacher
D000818:Animals; D001665:Binding Sites; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D006801:Humans; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D013057:Spectrum Analysis / Q000379:methods; D013379:Substrate Specificity
D003577:Cytochrome P-450 Enzyme System