Inhibitor-induced conformational change in cytochrome P-450CAM.

The X-ray crystal structures of cytochrome P-450 CAM complexed with both enantiomers of a chiral, multifunctional inhibitor have been refined to R-factors of 21.0% [(+)-enantiomer] and 19.6% [(-)-enantiomer] at approximately 2.1-A resolution. Binding of either enantiomer, both considerably larger than the natural substrate camphor, results in similar, dramatic structural changes in the enzyme. In contrast to all previous P-450 CAM crystallographic structures, the Tyr96 side chain is not pointing «down» toward the heme but is rather directed «up» into the proposed substrate access channel