Quantitative structure-activity relationship based quantification of the impacts of enzyme-substrate binding on rates of peroxidase-mediated reactions of estrogenic phenolic chemicals.
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.
Environmental and Water Resources Engineering Program and Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109-2099, USA.
Lisa M
LM
Colosi
Qingguo
Q
Huang
Walter J
WJ
Weber
D004967:Estrogens / Q000737:chemistry* / Q000378:metabolism*; D006735:Horseradish Peroxidase / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D010636:Phenols / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D013379:Substrate Specificity
D004967:Estrogens; D010636:Phenols; D006735:Horseradish Peroxidase