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F. Johnson these ion pairs are broken, which frees Asp251 to serve its proposed role in shuttling protons from bulk solvent into the active site It thus appears that an important part of Pdx binding may be to “arm” the proton delivery machinery required for proton-coupled electron transfer The next obvious question is whether or not this sort of redox partner-mediated conformational change required for activity is a general property of all P450s or is limited to P450cam The weight of the evidence so far indicates that P450cam may be an outlier A number of P450s are known to be supported by nonphysiological redox partners and some redox partners, such as P450 reductase, service a large number of P450s The only structural comparisons that can be made to address this question are the P450cam–Pdx and CYP11A1–Adx complexes [69] CYP11A1 does not change to the open form in the complex but remains closed [69, 70] However, Asp290 (corresponds to Asp251 in P450cam) is not tied up in ion pairs and is exposed to bulk solvent Hence, no structural changes are required to free Asp290 for catalysis, although it has yet to be established if Asp290 is essential for CYP11A1 catalysis Given that Nature has so many P450s, it is doubtful that P450cam is the only P450 where selective redox partner binding coupled with conformational selection is required for activity It should only be a matter of time before similar P450s are uncovered and analyzed in depth Just as interesting a question is the biological basis for such control What is the evolutionary advantage, if any, of P450cam exhibiting such specificity, while very closely related P450s do not?

Poulos and E. F. 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