Multifunctionality analysis of serine hydroxymethyltransferases from human and Escherichia coli

Serine hydroxymethyltransferase (SHMT) catalyzes the conversion of l-serine and tetrahydrofolate (THF) to glycine and 5,10-methylenetetrahydrofolate, respectively. In a previous study, we found that human and Escherichia coli SHMTs possess THF-dependent d-serine dehydratase activity, which degrades d-serine to pyruvate and ammonia. Some activities including aldolase and racemase activities have also been reported for SHMTs. In the present study, we investigated the multifunctionality of E. coli SHMT and two human SHMTs. All three SHMTs displayed high aldolase activity toward l-allo-threonine and l-threo-phenylserine, and measurable activity toward l-threonine, but they did not act on d-allo-threonine and d-threonine. The catalytic efficiency (k_cat/K_m) for l-allo-threonine was higher than for l-threo-phenylserine. None of the SHMTs displayed racemase activity toward various amino acids, although slight alanine racemase activity was detected for E. coli SHMT. Likewise, none of the SHMTs showed lyase, aminotransferase, or aspartate decarboxylase activities, and none exhibited dehydratase activity toward other hydroxy amino acids except d-serine. SHMTs are multifunctional enzymes possessing canonical hydroxymethyltransferase, d-serine dehydratase, and low-specificity l-threonine aldolase activities.