5a01: Difference between revisions
New page: '''Unreleased structure''' The entry 5a01 is ON HOLD Authors: Mariappa, D., Zheng, X., Schimpl, M., Raimi, O., Rafie, K., Ferenbach, A.T., Mueller, H.J., van Aalten, D.M.F. Description... |
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==O-GlcNAc transferase from Drososphila melanogaster== | |||
<StructureSection load='5a01' size='340' side='right'caption='[[5a01]], [[Resolution|resolution]] 2.66Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5a01]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5A01 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5A01 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.66Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=12V:(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'>12V</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5a01 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5a01 OCA], [https://pdbe.org/5a01 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5a01 RCSB], [https://www.ebi.ac.uk/pdbsum/5a01 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5a01 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q7KJA9_DROME Q7KJA9_DROME] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
Dual functionality of O-GlcNAc transferase is required for Drosophila development.,Mariappa D, Zheng X, Schimpl M, Raimi O, Ferenbach AT, Muller HA, van Aalten DM Open Biol. 2015 Dec;5(12):150234. doi: 10.1098/rsob.150234. PMID:26674417<ref>PMID:26674417</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Ferenbach | <div class="pdbe-citations 5a01" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Glycosyltransferase 3D structures|Glycosyltransferase 3D structures]] | ||
[[Category: | *[[O-GlcNAc transferase 3D structures|O-GlcNAc transferase 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: Drosophila melanogaster]] | |||
[[Category: Large Structures]] | |||
[[Category: Ferenbach AT]] | |||
[[Category: Mariappa D]] | |||
[[Category: Mueller HJ]] | |||
[[Category: Rafie K]] | |||
[[Category: Raimi O]] | |||
[[Category: Schimpl M]] | |||
[[Category: Zheng X]] | |||
[[Category: Van Aalten DMF]] | |||
Latest revision as of 14:01, 10 January 2024
O-GlcNAc transferase from Drososphila melanogasterO-GlcNAc transferase from Drososphila melanogaster
Structural highlights
FunctionPublication Abstract from PubMedPost-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. Dual functionality of O-GlcNAc transferase is required for Drosophila development.,Mariappa D, Zheng X, Schimpl M, Raimi O, Ferenbach AT, Muller HA, van Aalten DM Open Biol. 2015 Dec;5(12):150234. doi: 10.1098/rsob.150234. PMID:26674417[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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