1phf
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CRYSTAL STRUCTURES OF METYRAPONE-AND PHENYLIMIDAZOLE-INHIBITED COMPLEXES OF CYTOCHROME P450-CAM
OverviewOverview
The crystal structures of metyrapone- and 1-, 2-, and, 4-phenylimidazole-inhibited complexes of cytochrome P-450cam have been, refined to a nominal resolution of 2.1 A and compared with the 1.63-A, camphor-bound structure. With the exception of 2-phenylimidazole, each of, the inhibitors forms an N-Fe bond with the heme iron atom while part of, the inhibitor sits in the camphor-binding pocket. In the 2-phenylimidazole, complex, a water molecule or hydroxide ion coordinates with the heme iron, atom while the inhibitor binds in the camphor pocket adjacent to the aqua, ligand. Each of the inhibitors forces the central region of helix I that, forms part of the O2 binding pocket to move away from the inhibitor, with, the exception of 2-phenylimidazole where the helix moves in toward the, inhibitor. In addition, the Tyr-96 region, which provides specific contact, points with the substrate, is perturbed, although to varying degrees with, each inhibitor. These perturbations include large, localized changes in, Debye-Waller or temperature factors, indicative of changes in dynamical, fluctuations. The largest inhibitor, metyrapone, causes the fewest, changes, while 2-phenylimidazole binding causes the largest, especially in, helix I. The large 2-phenylimidazole-induced movement of helix I can be, rationalized on the basis of the inhibitor imidazole group's, hydrogen-bonding requirements.
About this StructureAbout this Structure
1PHF is a Single protein structure of sequence from Pseudomonas putida with HEM and PIM as ligands. Active as Camphor 5-monooxygenase, with EC number 1.14.15.1 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of metyrapone- and phenylimidazole-inhibited complexes of cytochrome P-450cam., Poulos TL, Howard AJ, Biochemistry. 1987 Dec 15;26(25):8165-74. PMID:3442650
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