biostudies-literatureBallard CJFondo Europeo de Desarrollo RegionalComplex Carbohydrate Research Center, University of GeorgiaMinistry of Education and ScienceNCI NIH HHSNational Institutes of HealthNIH HHSNIGMS NIH HHSDanish National Research FoundationGobierno de Aragón817-836https://www.ebi.ac.uk/biostudies/studies/S-EPMC10629720biostudies-literatureUnknown33(10)A large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) initiate mucin type O-glycosylation transferring α-GalNAc from a UDP-GalNAc donor to the hydroxyl groups of Ser and Thr residues of peptides and proteins, thereby defining sites of O-glycosylation. Mutations and differential expression of several GalNAc-Ts are associated with many disease states including cancers. The mechanisms by which these isozymes choose their targets and their roles in disease are not fully understood. We previously showed that the GalNAc-Ts possess common and unique specificities for acceptor type, peptide sequence and prior neighboring, and/or remote substrate GalNAc glycosylation. In the present study, the role of flanking charged residues was investigated using a library of charged peptiGlycobiologyPolypeptide N-acetylgalactosaminyltransferase (GalNAc-T) isozyme surface charge governs charge substrate preferences to modulate mucin type O-glycosylation.PMC10629720P01-GM107012R01 CA078834E34_R17LMP58_18R01 GM113534P41-GM103390PID2019-105451GB-I002014–2020R01-GM113534P01 GM107012P41 GM103390DNRF107Hurtado-Guerrero RBallard CJPaul Daniel EJGerken TAPaserba MRfalsePolypeptide N-acetylgalactosaminyltransferase (GalNAc-T) isozyme surface charge governs charge substrate preferences to modulate mucin type O-glycosylation.A large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) initiate mucin type O-glycosylation transferring α-GalNAc from a UDP-GalNAc donor to the hydroxyl groups of Ser and Thr residues of peptides and proteins, thereby defining sites of O-glycosylation. Mutations and differential expression of several GalNAc-Ts are associated with many disease states including cancers. The mechanisms by which these isozymes choose their targets and their roles in disease are not fully understood. We previously showed that the GalNAc-Ts possess common and unique specificities for acceptor type, peptide sequence and prior neighboring, and/or remote substrate GalNAc glycosylation. In the present study, the role of flanking charged residues was investigated using a library of charged pepti2023-01-01T00:00:00Z2023 Oct2026-04-19T03:24:51.712Z2025-06-01T12:02:46.59ZS-EPMC106297203755566910.1093/glycob/cwad066