PMID: 16829524

 

    Legend: Sugar

Title : X-ray crystal structure of leukocyte type core 2 beta1,6- N-acetylglucosaminyltransferase

Abstract :

1. Evidence for a convergence of metal ion-independent glycosyltransferase mechanism
2. Leukocyte type core 2 beta1,6- N-acetylglucosaminyltransferase ( C2GnT-L ) is a key enzyme in the biosynthesis of branched O-glycans
3. It is an inverting, metal ion-independent family 14 glycosyltransferase that catalyzes the formation of the core 2 O-glycan (Galbeta1-3[GlcNAcbeta1-6]GalNAc-O-Ser/Thr) from its donor and acceptor substrates, UDP-GlcNAc and the core 1 O-glycan (Galbeta1-3GalNAc-O-Ser/Thr), respectively
4. Reported here are the x-ray crystal structures of murine C2GnT-L in the absence and presence of the acceptor substrate Galbeta1-3GalNAc at 2.0 and 2.7A resolution, respectively
5. C2GnT-L was found to possess the GT-A fold; however, it lacks the characteristic metal ion binding DXD motif
6. The Galbeta1-3GalNAc complex defines the determinants of acceptor substrate binding and shows that Glu-320 corresponds to the structurally conserved catalytic base found in other inverting GT-A fold glycosyltransferases
7. Comparison of the C2GnT-L structure with that of other GT-A fold glycosyltransferases further suggests that Arg-378 and Lys-401 serve to electrostatically stabilize the nucleoside diphosphate leaving group, a role normally played by metal ion in GT-A structures
8. The use of basic amino acid side chains in this way is strikingly similar to that seen in a number of metal ion-independent GT-B fold glycosyltransferases and suggests a convergence of catalytic mechanism shared by both GT-A and GT-B fold glycosyltransferases