Biocatalysis and substrate chemodiversity: Adaptation of aerobic living organisms to their chemical environment

A unique family of proteins, the cytochromes P450, catalyze the oxidation of almost all the compounds of our environment, often called xenobiotics. They play a key role in the adaptation of aerobic living organisms to their always changing chemical environment. How a single family of catalysts can operate in a relatively efficient manner on such extremely diverse substrates? Recent X-ray structures of mammalian xenobiotic-metabolizing P450s (mainly from human liver) that have been published during the 2003-2007 period, allow one to begin to answer this question. These data have shown the great diversity of sizes, shapes, and modes of binding of the substrate binding sites of these mammalian cytochromes P450. They have also shown how conformationally flexible are these active sites, that can adapt themselves to the xenobiotic structure for the best possible efficacy of substrate oxidation Catalysis. (C) 2008 Elsevier B.V. All rights reserved.