Figure 2.

Secondary and tertiary structures of P450 proteins. (a) Topology diagram showing the secondary structure and arrangement of the secondary structural elements of a typical P450 protein (CYP102) [14]. Blue boxes, a helices; groups of cream arrows outlined with dotted lines, ß sheets; lines, coils and loops. The sizes of the elements are not in proportion to their length in the primary sequence. There are usually around four ß sheets and 13 a helices defining one domain that is predominantly ß sheets and one that is predominantly a helices. The first domain is often associated with substrate recognition and the access channel, the second with the catalytic center. Adapted from [14]. (b) A ribbon representation of the distal face of the folded CYP2C5 protein showing its putative association with the ER membrane (purple) [16]. Helices and sheets are labeled as in (a). Heme is in orange, the substrate in yellow. The a domain is on top left, the ß domain more closely associated with the membrane at bottom right. Epitopes not accessible for antibody binding when the protein is associated with the ER are shown in red (numbers give their position in the primary sequence). The transmembrane amino-terminal segment, removed for crystallization, and an additional II residues that are disordered in the crystal structure, are not shown. Note the I helix above the heme, close to the substrate-binding site. The heme-binding loop is visible behind the heme protoporphyrin. The conserved Gln-X-X-Arg structure in the K helix is also at the back and so is not readily visible. The proximal (back) face of the protein is involved in redox partner recognition and electron transfer to the active site; protons flow into the active site from the distal face (front). The substrate access channel is usually assumed to be located in close contact of the membrane between the F-G loop, the A helix and ß strands 1-1 and 1-2. More pictures showing other aspects of the structure, including reductase and substrate-binding, can be viewed at [17,18]. Another picture (a model) of membrane-bound P450 including the transmembrane domain can be seen at [36]. Reproduced with permission from [37].