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Publication Abstract from PubMed

Human beta1,3-galactosyltransferase 5 (beta3GalT5) is a key enzyme involved in the synthesis of glycans on glycoproteins and glycolipids that are associated with various important biological functions, especially tumor malignancy and cancer progression, and has been considered as a promising target for development of anticancer agents. In this study, we determined the X-ray structures of beta3GalT5 in complex with the stable donor analogue UDP-2-fluorogalactose or the native donor substrate UDP-galactose (UDP-Gal) and several glycan acceptors at different reaction steps. Based on the structures obtained from our experiments, beta3GalT5 catalyzes the transfer of galactose from UDP-Gal to a broad spectrum of glycan acceptors with an S(N)2-like mechanism; however, in the absence of a glycan acceptor, UDP-Gal is slowly converted to UDP and two other products, one is galactose through an S(N)2-like mechanism with water as an acceptor and the other is an oxocarbenium-like product, presumably through an S(N)1-like mechanisms. The structure, mechanism, and specificity of beta3GalT5 presented in this study advance our understanding of enzymatic glycosylation and provide valuable insights for application to glycan synthesis and drug design targeting beta3GalT5-associated cancer.

Structure-Based Mechanism and Specificity of Human Galactosyltransferase beta3GalT5.,Lo JM, Kung CC, Cheng TR, Wong CH, Ma C J Am Chem Soc. 2025 Apr 2;147(13):10875-10885. doi: 10.1021/jacs.4c11724. Epub , 2025 Mar 25. PMID:40130308^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.