Cytosolic sulfotransferases (SULTs) are a family of enzymes which catalyze the transfer of a sulfuryl group from a donor, usually 3′-phosphoadenosine 5′-phosphosulfate (PAPS), to an acceptor molecule with an amino or hydroxyl group. Sulfoconjugation is an important process in the human body as it can increase the solubility of the molecules, facilitate excretion, and act as a mechanism for regulation of neurotransmitter and hormone levels. Despite being an important class of metabolic enzymes, our knowledge of their substrate specificity is somewhat lacking. Of particular interest is SULT1A3, which shares a considerable amount of its amino acid sequence and structure with SULT1A1 and yet demonstrates a unique biological function and substrate preference whose basis is not well understood. While SULT1A1 preferentially catalyzes the reaction in simple phenols, such as <i>para-</i>nitrophenol, SULT1A3 has a strong affinity for catecholamines, such as dopamine. In order to gain better insight into this difference in specificity and selectivity, a library of dopamine analogues with various electron donating and withdrawing groups have been synthesized to analyze their binding affinities in each enzyme. SULT enzymatic assays will be utilized to evaluate the dopaminergic derivatives as substrates for SULT1A1 and SULT1A3 <i>in vitro</i>, and the sulfation reaction will be monitored via RP-HPLC. The comparison of the kinetic parameters of each substrate in SULT1A1 and SULT1A3 and its implications for the design and metabolism of drugs and biologically-relevant compounds will be discussed.

Investigation of the molecular basis of substrate selectivity in SULT1A1 and SULT1A3

2019 Spring National Meeting

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