Crystal structure of hemoprotein domain of P450BM-3, a prototype for microsomal P450's.
Cytochrome P450BM-3, a bacterial fatty acid monoxygenase, resembles the eukaryotic microsomal P450's and their flavoprotein reductase in primary structure and function. The three-dimensional structure of the hemoprotein 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 alph and a beta domain. The active site heme 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 substrate binding pocket. Substantial differences between P450BM-3 and P450cam, the only other P450 structure available, are observed around the substrate binding pocket and the regions important for redox partner binding. A general mechanism for proton transfer in P450's is also proposed.
Ravichandran
K G
KG
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas 75235-9050.
Boddupalli
S S
SS
Hasermann
C A
CA
Peterson
J A
JA
Deisenhofer
J
J
D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D001665:Binding Sites; D003196:Computer Graphics; D003460:Crystallization; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D006418:Heme / Q000737:chemistry; D006899:Mixed Function Oxygenases / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009251:NADPH-Ferrihemoprotein Reductase; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014961:X-Ray Diffraction
D001426:Bacterial Proteins; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D009251:NADPH-Ferrihemoprotein Reductase; C052423:flavocytochrome P450 BM3 monoxygenases