Beta-galactoside alpha-2,3-sialyltransferase (ST3Gal)

Beta-galactoside alpha-2,3-sialyltransferases (ST3Gal family) are Golgi-localized enzymes that catalyze the transfer of sialic acid from CMP-Neu5Ac to the terminal galactose of glycoproteins and glycolipids via an alpha-2,3 linkage. This family includes six members (ST3Gal I-VI) in humans, each with distinct substrate specificities for O-glycans, N-glycans, or gangliosides. These enzymes play a critical role in cell-cell recognition, adhesion, and signal transduction by modulating the sialylation patterns of the cell surface. In disease, overexpression of ST3Gal enzymes leads to hypersialylation, a hallmark of cancer that promotes metastasis, angiogenesis, and immune evasion by masking tumor cells from the immune system. Hypersialylation also contributes to resistance against certain cytotoxic drugs and facilitates viral entry for pathogens like influenza. Consequently, ST3Gal inhibitors like Lith-O-Asp and Soyasaponin I are being investigated as potential antimetastatic and anti-inflammatory agents. These inhibitors work by blocking the transfer of sialic acid, thereby reducing the expression of pro-metastatic antigens like Sialyl-Lewis X. Despite their potential, achieving subtype selectivity remains a significant challenge due to the high conservation of the catalytic domain across the ST3Gal family.

Other names

CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferaseSiaTN-acetyllactosaminide alpha-2,3-sialyltransferaseST3Gal IST3Gal IIST3Gal IIIST3Gal IVST3Gal VST3Gal VILactosylceramide alpha-2,3-sialyltransferaseGM3 synthaseAlpha-2,3-sialyltransferase

Inhibition of the transfer of sialic acid from the donor CMP-N-acetylneuraminate (CMP-Neu5Ac) to the terminal galactose residues of glycoproteins and glycolipids, thereby preventing the formation of alpha-2,3-linked sialoglycoconjugates.