We have studied the substrate selectivity of the sulfotransferase enzyme (SULT1A1) by both protein-ligand interactions in the active-site and by kinetics of proton abstraction. The sulfotransferase enzymes (SULTs) catalyze the addition of a sulfate group to a variety of small molecules, including neurotransmitters and xenobiotics. This reaction can activate or deactivate bio-active molecules or change their pharmacokinetic behavior. A set of dopamine analogs with substituents in the 6-position were chosen for study. In previous work, we have studied the interaction energies between the ligands and the amino-acids of the active-site using MP2 and M062X with 6-311+g*; these energies were used to determine the thermodynamic stability of the ligand in the active site. The addition of the sulfuryl group to the ligand depends on deprotonation of a phenol group on the ligand. Thus, the activation energies for proton abstraction from the ligand to the histidine residue were calculated for all ligands using M062x/6-31++g**. Our results show a strong dependence of the activation energy of the proton transfer on the substituent in the 6-position.

Kinetics of proton transfer for ligands in the SULT1A1 active site

251st National Meeting (2016)

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