1p2y

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(New page: 200px<br /><applet load="1p2y" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p2y, resolution 2.3&Aring;" /> '''CRYSTAL STRUCTURE OF ...)
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Revision as of 21:18, 20 November 2007


1p2y, resolution 2.3Å

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

Overview

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.

About this Structure

1P2Y is a Single protein structure of sequence from Pseudomonas putida with HEM and NCT as ligands. Active as Camphor 5-monooxygenase, with EC number 1.14.15.1 Full crystallographic information is available from OCA.

Reference

Crystallographic studies on the complex behavior of nicotine binding to P450cam (CYP101)., Strickler M, Goldstein BM, Maxfield K, Shireman L, Kim G, Matteson DS, Jones JP, Biochemistry. 2003 Oct 21;42(41):11943-50. PMID:14556625

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