Unknown

Dataset Information

0

Synergy of peptide and sugar in O-GlcNAcase substrate recognition.


ABSTRACT: Protein O-GlcNAcylation is an essential reversible posttranslational modification in higher eukaryotes. O-GlcNAc addition and removal is catalyzed by O-GlcNAc transferase and O-GlcNAcase, respectively. We report the molecular details of the interaction of a bacterial O-GlcNAcase homolog with three different synthetic glycopeptides derived from characterized O-GlcNAc sites in the human proteome. Strikingly, the peptides bind a conserved O-GlcNAcase substrate binding groove with similar orientation and conformation. In addition to extensive contacts with the sugar, O-GlcNAcase recognizes the peptide backbone through hydrophobic interactions and intramolecular hydrogen bonds, while avoiding interactions with the glycopeptide side chains. These findings elucidate the molecular basis of O-GlcNAcase substrate specificity, explaining how a single enzyme achieves cycling of the complete O-GlcNAc proteome. In addition, this work will aid development of O-GlcNAcase inhibitors that target the peptide binding site.

SUBMITTER: Schimpl M 

PROVIDER: S-EPMC3476531 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC8171356 | biostudies-literature
| S-EPMC5617298 | biostudies-literature
| S-EPMC7856287 | biostudies-literature
| S-EPMC4109824 | biostudies-literature
| S-EPMC3660302 | biostudies-literature
| S-EPMC4215262 | biostudies-literature
| S-EPMC5610315 | biostudies-literature
| S-EPMC4556313 | biostudies-literature
| S-EPMC3249425 | biostudies-literature
| S-EPMC5625900 | biostudies-literature