2D7R

Crystal structure of pp-GalNAc-T10 complexed with GalNAc-Ser on lectin domain

Summary for 2D7R

• Entry DOI: 10.2210/pdb2d7r/pdb
• Related: 2D7I
• Descriptor: Polypeptide N-acetylgalactosaminyltransferase 10, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: beta trefoil, rossmann fold, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 67345.73

Authors

Kubota, T.,Shiba, T.,Sugioka, S.,Kato, R.,Wakatsuki, S.,Narimatsu, H. (deposition date: 2005-11-25, release date: 2006-11-07, Last modification date: 2024-10-30)

Primary citation

Kubota, T.,Shiba, T.,Sugioka, S.,Furukawa, S.,Sawaki, H.,Kato, R.,Wakatsuki, S.,Narimatsu, H.
Structural basis of carbohydrate transfer activity by human UDP-GalNAc: polypeptide alpha-N-acetylgalactosaminyltransferase (pp-GalNAc-T10)
J.Mol.Biol., 359:708-727, 2006

PubMed Abstract: Mucin-type O-glycans are important carbohydrate chains involved in differentiation and malignant transformation. Biosynthesis of the O-glycan is initiated by the transfer of N-acetylgalactosamine (GalNAc) which is catalyzed by UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases (pp-GalNAc-Ts). Here we present crystal structures of the pp-GalNAc-T10 isozyme, which has specificity for glycosylated peptides, in complex with the hydrolyzed donor substrate UDP-GalNAc and in complex with GalNAc-serine. A structural comparison with uncomplexed pp-GalNAc-T1 suggests that substantial conformational changes occur in two loops near the catalytic center upon donor substrate binding, and that a distinct interdomain arrangement between the catalytic and lectin domains forms a narrow cleft for acceptor substrates. The distance between the catalytic center and the carbohydrate-binding site on the lectin beta sub-domain influences the position of GalNAc glycosylation on GalNAc-glycosylated peptide substrates. A chimeric enzyme in which the two domains of pp-GalNAc-T10 are connected by a linker from pp-GalNAc-T1 acquires activity toward non-glycosylated acceptors, identifying a potential mechanism for generating the various acceptor specificities in different isozymes to produce a wide range of O-glycans.

PubMed: 16650853
DOI: 10.1016/j.jmb.2006.03.061

Experimental method

X-RAY DIFFRACTION (2.8 Å)