Title: Quantitative structure-activity relationship based quantification of the impacts of enzyme-substrate binding on rates of peroxidase-mediated reactions of estrogenic phenolic chemicals.

Authors: Colosi, Lisa M; Huang, Qingguo; Weber Jr, Walter J

Published In J Am Chem Soc, (2006 Mar 29)

Abstract: The initial rates of horseradish peroxidase (HRP)-mediated enzymatic reactions of 15 assorted aqueous phase phenolic chemicals were studied. The associated reaction rate constants were found to correlate quantitatively with two independent variables: the highest-occupied molecular orbital energy (E(HOMO)) defining the intrinsic redox reactivities of the phenolic substrates and the distance between a substrate and the deltaN of HIS42's imidazole ring in an HRP/substrate binding complex, obtained through molecular simulations. Highly correlated quantitative structure-activity relationship (QSAR) equations were thus developed. This work provides insights into the impacts that HRP/substrate binding may have on HRP-mediated reactions. Additionally, the QSAR equations developed in the work may serve as a basis to further explore the potential use of HRP-mediated reactions in the treatment of estrogenic contaminants, and they constitute an important tool for redesign and screening of potential proteomic modifications to the wild-type HRP structure intended to enhance reactivity toward selected substrates.

PubMed ID: 16551113

MeSH Terms: Estrogens/chemistry*; Estrogens/metabolism*; Horseradish Peroxidase/chemistry*; Horseradish Peroxidase/metabolism*; Kinetics; Phenols/chemistry*; Phenols/metabolism*; Protein Conformation; Quantitative Structure-Activity Relationship; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Substrate Specificity