Validation of a two-parameter quantitative structure-activity relationship as a legitimate tool for rational re-design of horseradish peroxidase.
Previously reported rates of reaction between six mutant strains of the enzyme horseradish peroxidase (HRP) and a test substrate, 2-methoxyphenol, were found to correlate with characteristic binding distances computed using molecular simulation. The correlation (R(2) = 0.86) bears out a working hypothesis that, based on a quantitative structure-activity relationship (QSAR) we had previously developed for HRP, reductions in binding distances between the HRP enzyme and any selected substrate mediate increased enzyme reactivity towards that substrate. The results validate the use of QSAR as a quantitative means for formulating enzyme mutations designed to achieve enhanced HRP reactivity towards compounds of specific interest.
Department of Civil & Environmental Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.
Lisa M
LM
Colosi
Qingguo
Q
Huang
Walter J
WJ
Weber
D000595:Amino Acid Sequence; D003198:Computer Simulation; D015195:Drug Design; D004789:Enzyme Activation; D006735:Horseradish Peroxidase / Q000737:chemistry* / Q000648:ultrastructure*; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015202:Protein Engineering / Q000379:methods; D021281:Quantitative Structure-Activity Relationship; D020539:Sequence Analysis, Protein / Q000379:methods*
D006735:Horseradish Peroxidase