Sufficient structural information on mammalian cytochromes P450 has now been published (including seventeen X-ray structures of these enzymes by June 2006) to allow characteristic features of these enzymes to be identified, including: (i) the presence of a common fold, typical of all P450s, (ii) similarities in the positioning of the heme cofactor, (iii) the spatial arrangement of certain structural elements, and (iv) the access/egress paths for substrates and products, (v) probably common orientation in the membrane, (vi) characteristic properties of the active sites with networks of water molecules, (vii) mode of interaction with redox partners and (viii) a certain degree of flexibility of the structure and active site determining the ease with which the enzyme may bind the substrates. As well as facilitating the identification of common features, comparison of the available structures allows differences among the structures to be identified, including variations in: (i) preferred access/egress paths to/from the active site, (ii) the active site volume and (iii) flexible regions. The availability of crystal structures provides opportunities for molecular dynamic simulations, providing data that are apparently complementary to experimental findings but also allow the dynamic behavior of access/egress paths and other dynamic features of the enzymes to be explored.

Department of Physical Chemistry Faculty of Sciences Palacky University Svobody 26 771 46 Olomouc Czech Republic

Citace poskytuje Crossref.org

Identification of the N-terminal residues responsible for the differential microdomain localization of CYP1A1 and CYP1A2

Uncovering of cytochrome P450 anatomy by SecStrAnnotator

ChannelsDB: database of biomacromolecular tunnels and pores

The Role of Protein-Protein and Protein-Membrane Interactions on P450 Function

MOLE 2.0: advanced approach for analysis of biomacromolecular channels

CAVER 3.0: a tool for the analysis of transport pathways in dynamic protein structures

MOLEonline 2.0: interactive web-based analysis of biomacromolecular channels

Membrane position of ibuprofen agrees with suggested access path entrance to cytochrome P450 2C9 active site