1P7R: Crystal Structure Of Reduced, Co-Exposed Complex Of Cytochrome P450cam With (S)-(-)-Nicotine

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.
PDB ID: 1P7RDownload
MMDB ID: 25049
PDB Deposition Date: 2003/5/5
Updated in MMDB: 2003/11
Experimental Method:
x-ray diffraction
Resolution: 2.85  Å
Source Organism:
Similar Structures:
Biological Unit for 1P7R: monomeric; determined by author
Molecular Components in 1P7R
Label Count Molecule
Protein (1 molecule)
Cytochrome P450-cam
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB