2vsy
Xanthomonas campestris putative OGT (XCC0866), apostructureXanthomonas campestris putative OGT (XCC0866), apostructure
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPost-translational modification of protein serines/threonines with N-acetylglucosamine (O-GlcNAc) is dynamic, inducible and abundant, regulating many cellular processes by interfering with protein phosphorylation. O-GlcNAcylation is regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase, both encoded by single, essential, genes in metazoan genomes. It is not understood how OGT recognises its sugar nucleotide donor and performs O-GlcNAc transfer onto proteins/peptides, and how the enzyme recognises specific cellular protein substrates. Here, we show, by X-ray crystallography and mutagenesis, that OGT adopts the (metal-independent) GT-B fold and binds a UDP-GlcNAc analogue at the bottom of a highly conserved putative peptide-binding groove, covered by a mobile loop. Strikingly, the tetratricopeptide repeats (TPRs) tightly interact with the active site to form a continuous 120 A putative interaction surface, whereas the previously predicted phosphatidylinositide-binding site locates to the opposite end of the catalytic domain. On the basis of the structure, we identify truncation/point mutants of the TPRs that have differential effects on activity towards proteins/peptides, giving first insights into how OGT may recognise its substrates. Structural insights into mechanism and specificity of O-GlcNAc transferase.,Clarke AJ, Hurtado-Guerrero R, Pathak S, Schuttelkopf AW, Borodkin V, Shepherd SM, Ibrahim AF, van Aalten DM EMBO J. 2008 Oct 22;27(20):2780-8. Epub 2008 Sep 25. PMID:18818698[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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