5A01

O-GlcNAc transferase from Drososphila melanogaster

Summary for 5A01

• Entry DOI: 10.2210/pdb5a01/pdb
• Descriptor: O-GLYCOSYLTRANSFERASE, (2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-thiopyran-2-yl [(2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl dihydrogen diphosphate (3 entities in total)
• Functional Keywords: transferase, o-glcnac, protein posttranslational modification, tetratricopeptide repeats, glycosyltransferase, gt41, n-acetylglucosaminyltransferase, embryonic development
• Biological source: DROSOPHILA MELANOGASTER (FRUIT FLY)
• Total number of polymer chains: 3
• Total formula weight: 241021.49

Authors

Mariappa, D.,Zheng, X.,Schimpl, M.,Raimi, O.,Rafie, K.,Ferenbach, A.T.,Mueller, H.J.,van Aalten, D.M.F. (deposition date: 2015-04-15, release date: 2016-04-27, Last modification date: 2024-01-10)

Primary citation

Mariappa, D.,Zheng, X.,Schimpl, M.,Raimi, O.,Ferenbach, A.T.,Muller, H.A.,van Aalten, D.M.
Dual functionality of O-GlcNAc transferase is required for Drosophila development.
Open Biol, 5:150234-150234, 2015

PubMed Abstract: Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. OGT possesses a C-terminal glycosyltransferase catalytic domain and N-terminal tetratricopeptide repeats that are implicated in protein-protein interactions. Drosophila OGT (DmOGT) is encoded by super sex combs (sxc), mutants of which are pupal lethal. However, it is not clear if this phenotype is caused by reduction of O-GlcNAcylation. Here we use a genetic approach to demonstrate that post-pupal Drosophila development can proceed with negligible OGT catalysis, while early embryonic development is OGT activity-dependent. Structural and enzymatic comparison between human OGT (hOGT) and DmOGT informed the rational design of DmOGT point mutants with a range of reduced catalytic activities. Strikingly, a severely hypomorphic OGT mutant complements sxc pupal lethality. However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. Thus, OGT catalytic activity is required up to late pupal stages, while further development proceeds with severely reduced OGT activity.

PubMed: 26674417
DOI: 10.1098/rsob.150234

Experimental method

X-RAY DIFFRACTION (2.66 Å)