P450s: Structural similarities and functional differences

More than 400 identified P450s are found in prokaryotes and eukaryotes, plante and animals, mitochondria and endoplasmic reticulum that function in areas such as xenobiotic metabolism and steroidogenesis. This superfamily of proteins has proved difficult to study because of the hydrophobic nature of their substrates, their various redox partners, and the membrane association of the eukaryotic proteins. To better understand the structure/function relationship of P450s–what determines substrate specificity and selectivity, what determines redox partner binding, and which regions are involved in membrane binding–we have compared the three crystallized, soluble bacterial P450s (two class I and one class II) and a model of a steroidogenic, eukaryotic P450 (P450arom) in order to define which structural elements form a conserved struc‐tural fold for P450s, what determines specificity of substrate binding and redox partner binding, and which regions are potentially involved in membrane association. We believe there is a conserved structural fold for all P450s that can be used to model those P450s that prove intransigent to structural determination. However, although there appears to be a conserved structural core among P450s, there is sufficient sequence variability that no two P450s are structurally identical.—Graham‐Lorence, S., Peterson, J. A. P450s: Structural similarities and functional differences. FASEB J. 10, 206‐214 (1996)