Glycobiology Advance Access published online on November 1, 2002
Glycobiology, doi:10.1093/glycob/cwg007
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© 2002 Oxford University Press
MINI REVIEWS
1 Biological Chemistry Section, National Institute of Diabetes & Digestive & Kidney Diseases, NIH, Bethesda, MD. 20892 Mucin-type linkages (GalNAc
"All in the Family" - The UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases
1,O-Ser/Thr) are initiated by a family of glycosyltransferases termed the UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferases (ppGaNTases, E.C. 2.4.1.41). These enzymes transfer GalNAc from the sugar donor UDP-GalNAc to serine and threonine residues forming an alpha anomeric linkage. Despite the seeming simplicity of ppGaNTase catalytic function, it is estimated on the basis of in silico analysis that there are 24 unique ppGaNTase human genes. ppGaNTase isoforms display both tissue-specific expression in adult mammals as well as unique spatial and temporal patterns of expression during murine development. In vitro assays suggest that a subset of the ppGaNTases have overlapping substrate specificities, but at least two ppGaNTases (ppGaNTase-T7 and -T9 [now designated -T10]) appear to require the prior addition of GalNAc to a synthetic peptide before they can catalyze sugar transfer to this substrate. Site-specific O-glycosylation by several ppGaNTases is influenced by the position and structure of previously added O-glycans. Collectively, these observations argue in favor of a hierarchical addition of core GalNAc residues to the apomucin. Various forms of O-glycan pathobiology may now be reexamined in light of the existence of an extensive ppGaNTase family of enzymes. Recent work has demonstrated at least one ppGaNTase isoform is required for normal development in D. melanogaster. Structural insights will no doubt lead to the development of isoform-specific inhibitors. Such tools will prove valuable to furthering our understanding of the functional roles played by O-glycans.
Key Words: O-glycosylation/O-linked oligosaccharides/UDP GalNAc:polypeptide N-acetylgalactosaminyltransferases/ UDP GalNAc
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