CoMFA modeling of enzyme kinetics: K(m) values for sulfation of diverse phenolic substrates by human catecholamine sulfotransferase SULT1A3.

Three-dimensional QSAR models were developed for predicting kinetic Michaelis constant (Km) values for phenolic substrates of human catecholamine sulfating sulfotransferase (SULT1A3). The Km values were correlated to the steric and electronic molecular fields of the substrates utilizing Comparative Molecular Field Analysis (CoMFA). The evaluated SULT1A3 substrate data set consisted of 95 different substituted phenols, catechols, catecholamines, steroids, and related structures for which the Km values were available. The data set was divided in three different subgroups in the initial analysis:  (1) for the first CoMFA model substrates with only one reacting hydroxyl group were selected (n = 51), (2) the second model was build with structurally rigid substrates (n = 59), and (3) finally all substrates of the data set were included in the analysis (n = 95). Substrate molecules were aligned using the aromatic ring and the reacting hydroxyl group as a template. After the initial analysis different substrate a...