Title : The beginnings of mucin biosynthesis: the crystal structure of UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferase-T1
Abstract :
- UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases (ppGaNTases) initiate the formation of mucin-type, O-linked glycans by catalyzing the transfer of alpha-N-acetylgalactosamine from UDP-GalNAc to Ser or Thr residues of core proteins to form the Tn antigen (GalNAc-alpha-1-O-Ser/Thr)
- 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 Mn2+ 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 (alpha, beta, and gamma) 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 alpha 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
Output (sent_index, trigger,
protein,
sugar,
site):
- 1. Ser, , -, -, Thr residues
- 5. domain, , -, the three potential lectin domain carbohydrate-binding sites, -
- 5. located, , -, the three potential lectin domain carbohydrate-binding sites, face
- 6. glycopeptide, , -, -, glycopeptide
Output(Part-Of) (sent_index,
protein,
site):
- 1. proteins, Ser
- 1. proteins, Thr residues
- 5. enzyme, face
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):