P450S - STRUCTURAL SIMILARITIES AND FUNCTIONAL DIFFERENCES

More than 400 identified P450s are found in prokaryotes and eukaryotes , plants and animals, mitochondria and endoplasmic reticulum that func tion in areas such as xenobiotic metabolism and steroidogenesis. This superfamily of proteins has proved difficult to study because of the h ydrophobic nature of their substrates, their various redox partners, a nd the membrane association of the eukaryotic proteins, To better unde rstand the structure/function relationship of P450s-what determines su bstrate specificity and selectivity, what determines redox partner bin ding, and which regions are involved in membrane binding-we have compa red the three crystallized, soluble bacterial P450s (two class I and o ne class II) and a model of a steroidogenic, eukaryotic P450 (P450arom ) in order to define which structural elements form a conserved struct ural 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 fo ld for all P450s that can be used to model those P450s that prove intr ansigent to structural determination. However, although there appears to be a conserved structural core among P450s, there is sufficient seq uence variability that no two P450s are structurally identical.