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.