Validation of a quantitative structure-activity relationship as means to redesign an enzyme for enhanced pollutant degradation

ENVR 147

Lisa M. Colosi, lmcolosi@umich.edu, Environmental & Water Resources Engineering Program, University of Michigan, Ann Arbor, 2200 Bonisteel Blvd. Rm 1234, Ann Arbor, MI 48109, Qingguo Huang, Department of Crop and Soil Sciences, University of Georgia, and Walter J. Weber Jr., Department of Chemical Engineering, University of Michigan, 2200 Bonisteel Rm 4013, Ann Arbor, MI 48109-2099.
Phenolic chemicals present in drinking water may elicit physiological responses similar to endogenous estrogen even at very low concentrations. Many of these chemicals are also substrates of the enzyme horseradish peroxidase (HRP). Unfortunately, smaller more weakly estrogenic substrates are more efficiently degraded than larger, more potent estrogens (i.e., 17β-estradiol). Because differential HRP activity has been attributed to poor enzyme-substrate binding, as parameterized using a quantitative structure activity relationship (QSAR), six previously-documented HRP mutants were investigated in a computational study of enzyme-substrate binding. Resulting simulation-predicted binding distances correlate with literature rates of reaction between mutants and test substrate, 2-methoxyphenol. This correlation (R2 = 0.86) bears out a hypothesis, based on the QSAR, that reduction in binding distance between HRP and any selected substrate mediates increased HRP reactivity towards that substrate. In a larger sense, results validate use of QSARs as means to formulate mutations designed to enhance reactivity towards priority pollutants.