Conformational dynamics in cytochrome P450-substrate interactions.
There now are four known cytochrome P450 crystal structures. Two of these, P450cam and P450eryF, are substrate-bound while P450terp and the heme domain of P450BM-3 are substrate-free. Here we describe a preliminary analysis of the P450BM-3 heme domain complexed with the 16-carbon fatty acid substrate, palmitoleic acid. A comparison of the substrate-free and -bound structures shows that a large conformational change in the substrate access channel accompanies substrate binding. This new information, together with the substrate-bound structures of P450cam and P450eryF, reveals which regions of P450 are the most important in controlling the dynamics of substrate binding and recognition.
Li
H
H
Department of Molecular Biology and Biochemistry, University of California at Irvine 92697, USA.
Poulos
T L
TL
D001426:Bacterial Proteins; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism*; D006418:Heme; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000378:metabolism*; D015394:Molecular Structure; D009251:NADPH-Ferrihemoprotein Reductase; D011487:Protein Conformation; D013379:Substrate Specificity
D001426:Bacterial Proteins; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D009251:NADPH-Ferrihemoprotein Reductase; C052423:flavocytochrome P450 BM3 monoxygenases