Recognition of the acceptor β-d-Glc pNAc-(1 → 2)-α-d-Manp(1 → 6)-β-d-Glc p-OR by N-acetylglucosaminyltransferase-V: None of the hydroxyl groups on the Glc-residue are important

✍ Scribed by Torsten Linker; Suzanne C. Crawley; Ole Hindsgaul

• Publisher: Elsevier Science
• Year: 1993
• Tongue: English
• Weight: 673 KB
• Volume: 245
• Category: Article
• ISSN: 0008-6215
• DOI: 10.1016/0008-6215(93)80081-o

✦ Synopsis

The enzyme, N-acetylglucosaminyltransferase-V (GlcNAcT-V, E.C 2.4.1.1551, transfers a P-D-GlcpNAc residue, from UDP-GlcNAc, to the OH-6 group of the Man residue in the synthetic acceptor P-D-GlcpNAc-(1 -+ 2)-cu-D-Manp-(I + ~)-~~-D-G~c~-G(CI-I,),CH~ (31. Trisaccharide 3 is an excellent substrate for the enzyme from hamster kidney with a K, value of 26 FM. In this paper we examine the contribution of the Glc residue in 3 to acceptor recognition by this enzyme. /.?-D-GlcpNAc-(1 + 2)-cu-D-Manp-O(CH,),CH,

(5), where the Glc residue in 3 has been deleted, was synthesized and found to be a very poor substrate with a K, value elevated to almost 2 mM. Two other analogues of 3, where the Glc residue was O-trimethylated (6) or 0-tribenzylated (71, respectively, possessed K, values very near to those of 3. The Glc residue in 3 is thereby shown to present an important recognition element for GlcNAcT-V, but none of the free hydroxyl groups are required. This observation should facilitate the design of more hydrophobic and membrane-permeable analogues of 3 that are expected to function as specific glycosylation inhibitors.