Projects per year
Abstract
O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. Although this enzyme modifies hundreds of proteins with O-GlcNAc, it is not understood how OGT achieves substrate specificity. In this study, we describe the application of a high-throughput OGT assay to a library of peptides. We mapped sites of O-GlcNAc modification by electron transfer dissociation MS and found that they correlate with previously detected O-GlcNAc sites. Crystal structures of four acceptor peptides in complex with Homo sapiens OGT suggest that a combination of size and conformational restriction defines sequence specificity in the â '3 to +2 subsites. This work reveals that although the N-terminal TPR repeats of OGT may have roles in substrate recognition, the sequence restriction imposed by the peptide-binding site makes a substantial contribution to O-GlcNAc site specificity.
Original language | English |
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Pages (from-to) | 744-749 |
Number of pages | 6 |
Journal | Nature Structural & Molecular Biology |
Volume | 22 |
Issue number | 9 |
DOIs | |
Publication status | Published - Sept 2015 |
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology
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Dive into the research topics of 'The active site of O-GlcNAc transferase imposes constraints on substrate sequence'. Together they form a unique fingerprint.Projects
- 1 Finished
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Aref#d: 21318. Molecular Mechanisms of O-GlcNAc Signalling (Senior Fellowship Renewal)
van Aalten, D. (Investigator)
1/06/09 → 29/02/16
Project: Research
Student theses
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Developing O-GlcNAc transferase inhibitors - insights from substrate recognition
Rafie, K. (Author), van Aalten, D. (Supervisor), 2017Student thesis: Doctoral Thesis › Doctor of Philosophy
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Profiles
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van Aalten, Daan
- Molecular Cell and Developmental Biology - Professor of Biological Chemistry
Person: Academic