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PDBsum entry 5a01
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References listed in PDB file
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Key reference
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Title
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Dual functionality of o-Glcnac transferase is required for drosophila development.
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Authors
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D.Mariappa,
X.Zheng,
M.Schimpl,
O.Raimi,
A.T.Ferenbach,
H.A.Müller,
D.M.Van aalten.
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Ref.
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Open Biol, 2015,
5,
150234.
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PubMed id
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Abstract
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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.
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