CMP-N-acetylneuraminate-beta-galactosyl-1,3-N-acetylgalactosaminide alpha-2,3-sialyltransferase 1 (ST3GAL1) (ST3Gal1 or ST3Gal-I)

ST3Gal1 is an inverting glycosyltransferase enzyme that catalyzes the transfer of sialic acid residues from the donor substrate CMP-Neu5Ac (CMP-N-acetylneuraminic acid) to acceptor substrates containing a terminal galactose residue[1]. The enzyme specifically recognizes the core 1 oligosaccharide motif Galβ1-3GalNAc found in Ser/Thr O-glycans of glycoproteins and ganglio-series glycolipids, forming α2,3 linkages[1][3]. ST3Gal1 belongs to the GT29 family of sialyltransferases and assumes a GT-A fold structure[3]. The enzyme operates through a direct displacement SN2-like mechanism, with histidine residues H299 and H316 acting as acid and base catalysts respectively[1]. Key residues including Y191, Y230, N147, S148, N170, and Y266 contribute to donor and acceptor substrate binding through hydrogen bonds and stacking interactions[1]. The catalytic site contains conserved motifs including the HP (His-Pro) motif and maintains activity through proper formation of disulfide bonds[1][3]. Overexpression of ST3Gal1 leads to hypersialylation of cell-surface glycoconjugates, a cancer-associated condition that promotes cell growth, migration, and invasion[1]. In ovarian cancer, upregulation of this enzyme is specifically linked to cancer progression, metastasis, and contributes to chemotherapy resistance[1][5]. The enzyme shows strict regioselectivity and substrate preference, with an optimal pH between 6 and 6.5, and does not require metal ions for activity[3]. ST3Gal1 preferentially acts on acceptors with the Galβ1-3GalNAc structure in both core 1 and core 2 O-glycans, with apparent Km values in the range of 0.05-0.2 mM for various acceptor substrates[3].

Other names

hST3Gal1 (human ST3Gal1)ST3Gal IST3Gal-Iα2,3-sialyltransferase ST3Gal1Sialyltransferase 1Core 1 sialyltransferase

Catalytic inhibition to prevent hypersialylation; Blockade of sialic acid transfer to reduce cancer cell metastasis