Dimerization is responsible for the structural stability of human sulfotransferase 1A1.

Cytosolic sulfotransferases (SULTs) are responsible for the metabolism of a variety of drugs, xenobiotics, and endogenous compounds. Most cytosolic SULTs are found to be homodimers. However, transformation between monomeric and dimeric SULTs can be achieved by a single amino acid mutation. The importance of quaternary structure for cytosolic sulfotransferase was investigated using recombinant human SULT1A1, a homodimer, and its monomeric mutant (V270E). The differences between dimeric and monomeric SULT1A1 were examined by size-exclusion liquid chromatography, enzyme kinetics, substrate binding affinity, thermal inactivation, conformational stability, and circular dichroism. Variations, especially on their secondary structures and stability, between homodimer and monomer of human SULT1A1 were observed. It was found that the active site of SULT1A1 was not significantly perturbed after the change of its quaternary structure according to SULT1A1 kinetics and substrate binding affinity. However, the stability of monomeric SULT1A1 is significantly decreased. We proposed that the importance of human SULT1A1 as a homodimer was to maintain its structural stability, and the change of secondary structure was responsible for alternating its quaternary structure.