2XGM

Substrate and product analogues as human O-GlcNAc transferase inhibitors.

Summary for 2XGM

• Entry DOI: 10.2210/pdb2xgm/pdb
• Related: 2JLB 2VSY 2XGO 2XGS
• Descriptor: XCOGT, ALLOXAN (3 entities in total)
• Functional Keywords: transferase
• Biological source: XANTHOMONAS CAMPESTRIS
• Total number of polymer chains: 2
• Total formula weight: 123133.52

Authors

Dorfmueller, H.C.,Borodkin, V.S.,Blair, D.E.,Pathak, S.,Navratilova, I.,van Aalten, D.M. (deposition date: 2010-06-07, release date: 2010-08-25, Last modification date: 2024-05-08)

Primary citation

Dorfmueller, H.C.,Borodkin, V.S.,Blair, D.E.,Pathak, S.,Navratilova, I.,Van Aalten, D.M.
Substrate and Product Analogues as Human O-Glcnac Transferase Inhibitors.
Amino Acids, 40:781-, 2011

PubMed Abstract: Protein glycosylation on serine/threonine residues with N-acetylglucosamine (O-GlcNAc) is a dynamic, inducible and abundant post-translational modification. It is thought to regulate many cellular processes and there are examples of interplay between O-GlcNAc and protein phosphorylation. In metazoa, a single, highly conserved and essential gene encodes the O-GlcNAc transferase (OGT) that transfers GlcNAc onto substrate proteins using UDP-GlcNAc as the sugar donor. Specific inhibitors of human OGT would be useful tools to probe the role of this post-translational modification in regulating processes in the living cell. Here, we describe the synthesis of novel UDP-GlcNAc/UDP analogues and evaluate their inhibitory properties and structural binding modes in vitro alongside alloxan, a previously reported weak OGT inhibitor. While the novel analogues are not active on living cells, they inhibit the enzyme in the micromolar range and together with the structural data provide useful templates for further optimisation.

PubMed: 20640461
DOI: 10.1007/S00726-010-0688-Y

Experimental method

X-RAY DIFFRACTION (2.55 Å)