A malleable catalyst dominates the metabolism of drugs

n this issue of PNAS, Ekroos and Sjo gren (1) present new structures of a cytochrome P450 (P450, or ''CYP''), in one case bound with two ligands. The results are of considerable importance not only in regard to the practical issues in drug development but also because they have general significance in consideration of the flexibility of enzymes in recognizing substrates. The concept of how some enzymes accommodate a broad variety of ligands and catalyze multiple, regioselective reactions on a single substrate is a challenge to a classical lock-and-key model of catalysis. The current work has broad implications for a number of important enzyme systems and how we understand them.