1P2Y

CRYSTAL STRUCTURE OF CYTOCHROME P450CAM IN COMPLEX WITH (S)-(-)-NICOTINE

Summary for 1P2Y

• Entry DOI: 10.2210/pdb1p2y/pdb
• Descriptor: Cytochrome P450-cam, PROTOPORPHYRIN IX CONTAINING FE, (S)-3-(1-METHYLPYRROLIDIN-2-YL)PYRIDINE, ... (4 entities in total)
• Functional Keywords: oxidoreductase, monooxygenase, heme, nicotine
• Biological source: Pseudomonas putida
• Cellular location: Cytoplasm (By similarity): P00183
• Total number of polymer chains: 1
• Total formula weight: 48196.47

Authors

Strickler, M.,Goldstein, B.M.,Maxfield, K.,Shireman, L.,Kim, G.,Matteson, D.,Jones, J.P. (deposition date: 2003-04-16, release date: 2003-10-28, Last modification date: 2024-02-14)

Primary citation

Strickler, M.,Goldstein, B.M.,Maxfield, K.,Shireman, L.,Kim, G.,Matteson, D.,Jones, J.P.
Crystallographic Studies on the Complex Behavior of Nicotine Binding to P450cam (CYP101)(dagger).
Biochemistry, 42:11943-11950, 2003

PubMed Abstract: Crystallographic and spectroscopic studies have been undertaken to characterize the binding behavior of the non-native substrate nicotine in the active site of the monooxygenase hemoprotein cytochrome P450cam. Despite the existence of a theoretical model that is consistent with the observed distribution of monooxygenation products, the crystal structure of the complex indicates that the primary binding mode of nicotine is unproductive. The structure is confirmed by spectral data that indicate direct coordination of substrate pyridine nitrogen with the heme iron. This would be the proper structure for evaluating binding affinity and inhibition. Reduction of the heme from Fe(III) to Fe(II) and introduction of carbon monoxide into crystals of the nicotine-P450cam complex, to simulate molecular oxygen binding, produces reorientation of the nicotine. This orientation is the appropriate one for predicting regioselectivity and the kinetic features of substrate oxidation. While it is not clear that such complicated behavior will be exhibited for other enzyme-substrate interactions, it is clear that a single crystal structure for a given substrate-enzyme interaction may not provide a good description of the binding mode responsible for product formation.

PubMed: 14556625
DOI: 10.1021/bi034833o

Experimental method

X-RAY DIFFRACTION (2.3 Å)