CRYSTAL-STRUCTURE OF HEMOPROTEIN DOMAIN OF P450BM-3, A PROTOTYPE FOR MICROSOMAL P450S

Cytochrome P450BM-3, a bacterial fatty acid monooxygenase, resembles t he eukaryotic microsomal P450's and their flavoprotein reductase in pr imary structure and function. The three-dimensional structure of the h emoprotein domain of P450BM-3 was determined by x-ray diffraction and refined to an R factor of 16.9 percent at 2.0 angstrom resolution. The structure consists of an alpha and a beta domain. The active site hem e is accessible through a long hydrophobic channel formed primarily by the beta domain and the B' and F helices of the alpha domain. The two molecules in the asymmetric unit differ in conformation around the su bstrate binding pocket. Substantial differences between P450BM-3 and P 450cam, the only other P450 structure available, are observed around t he substrate binding pocket and the regions important for redox partne r binding. A general mechanism for proton transfer in P450's is also p roposed.