ePrints

The mechanism of compound I formation revisited

Lookup NU author(s): Dr Peter Jones

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.

Abstract

The most recently proposed mechanisms for the formation of the Compound I intermediates of the peroxidases and catalases have been based on the crystallographic elucidation of the enzyme structures. It has been assumed that these mechanisms are compatible with an earlier proposal of the formation of a reversible enzyme-substrate intermediate called Compound 0, which was based on data that pre-dated the availability of the enzyme structures. However, it is argued here that this is not the case and some modifications of the existing mechanism are proposed which reconcile the structural, kinetic and energetic data for the reactions. This paper focuses attention on horseradish peroxidase isoenzyme C and particularly on the acid-base properties of the imidazole side chain of distal histidine 42. This imidazole group has an exceptionally low pKa value in the resting enzyme, which is higher in Compound I and higher still in Compound II. The pKa value must also be greatly increased following Compound 0 formation so that the imidazole can become an effective proton acceptor. An explanation is offered in a dielectric insertion (DI) model, in which the peroxide substrate, or fragments thereof, screens the influence of the positively charged heme iron on the pKa value of the imidazole group. It is proposed that Compound 0 is converted to a second intermediate, Compound 0*, by intramolecular proton transfer along a pre-existing hydrogen bond, a process which reduces the energy requirements of charge separation in the deprotonation of hydrogen peroxide. © 2005 Elsevier Inc. All rights reserved.

Publication metadata

Author(s): Jones P, Dunford HB

Publication type: Article

Publication status: Published

Journal: Journal of Inorganic Biochemistry

Year: 2005

Volume: 99

Issue: 12

Pages: 2292-2298

Print publication date: 01/12/2005

ISSN (print): 0162-0134

ISSN (electronic): 1873-3344

Publisher: Elsevier

URL: http://dx.doi.org/10.1016/j.jinorgbio.2005.08.009

DOI: 10.1016/j.jinorgbio.2005.08.009

PubMed id: 16213024

Altmetrics

Share