UDP-GalNAc:polypeptide ␣-N-acetylgalactosaminyltransferases (ppGaNTases) initiate the formation of mucin-type, O-linked glycans by catalyzing the transfer of ␣-N-acetylgalactosamine from UDP-GalNAc to Ser or Thr residues of core proteins to form the Tn antigen (GalNAc-␣-1-O-Ser͞Thr). ppGaNTases are unique among glycosyltransferases in containing a C-terminal lectin domain. We present the x-ray crystal structure of a ppGaNTase, murine ppGaNTase-T1, and show that it folds to form distinct catalytic and lectin domains. The association of the two domains forms a large cleft in the surface of the enzyme that contains a Mn 2؉ ion complexed by invariant D209 and H211 of the ''DXH'' motif and by invariant H344. Each of the three potential lectin domain carbohydrate-binding sites (␣, ␤, and ␥) is located on the active-site face of the enzyme, suggesting a mechanism by which the transferase may accommodate multiple conformations of glycosylated acceptor substrates. A model of a mucin 1 glycopeptide substrate bound to the enzyme shows that the spatial separation between the lectin ␣ site and a modeled active site UDP-GalNAc is consistent with the in vitro pattern of glycosylation observed for this peptide catalyzed by ppGaNTase-T1. The structure also provides a template for the larger ppGaNTase family, and homology models of several ppGaNTase isoforms predict dramatically different surface chemistries consistent with isoform-selective acceptor substrate recognition.glycosyltransferase ͉ mucin

By using molecular oxygen bis(μ‐oxo)dicopper(III) complexes can be produced from CuI complexes with ligand LX (LX=p‐substituted N‐ethyl‐N‐[2‐(2‐pyridyl)ethyl]‐2‐phenylethylamine; X=OMe, Me, H, Cl, NO2) in which the benzylic position of the ligand is activated and hydroxylated by the Cu2O2 core (see reaction scheme). Detailed characterization of this new C−H bond activation reaction by the bis(μ‐oxo)dicopper(III) core reveals important information on the fundamental chemistry underlying copper monooxygenase reactivity.