IRAZOQUI FERNANDO JOSE
Artículos
Título:
Functional control of polypeptide GalNAc-transferase 3 through an acetylation site in the C-terminal lectin domain
Autor/es:
LORENZ, VIRGINIA; CEJAS, RB; BENNETT EP; NORES, GA; IRAZOQUI FJ; IRAZOQUI, FJ
Revista:
BIOLOGICAL CHEMISTRY
Editorial:
WALTER DE GRUYTER & CO
Referencias:
Lugar: Berlin; Año: 2017
ISSN:
1431-6730
Resumen:
-GalNAc glycans are important structures in cellular homeostasis. Their biosynthesis is initiated by members of polypeptide GalNAc-transferase (ppGalNAc-T) enzyme family. Mutations in ppGalNAc-T3 isoform cause diseases (congenital disorders of glycosylation) in humans. The K626 residue located in the C-terminal β-trefoil fold of ppGalNAc-T3 was predicted to be a site with high likelihood of acetylation by CBP/p300 acetyltransferase. We used a site-directed mutagenesis approach to evaluate the role of this acetylation site in biological properties of the enzyme. Two K626 mutants of ppGalNAc-T3 (T3K626Q and T3K626A) had GalNAc-T activities lower than that of wild-type enzyme. Direct and competitive interaction assays revealed that GalNAc recognition by the lectin domain was altered in the mutants. The presence of GlcNAc glycosides affected the interaction of the three enzymes with mucin-derived peptides. In GalNAc-T activity assays, the presence of GlcNAc glycosides significantly i