Enzymes
UniProtKB help_outline | 850 proteins |
Reaction participants Show >> << Hide
- Name help_outline CTP Identifier CHEBI:37563 (Beilstein: 4732530) help_outline Charge -4 Formula C9H12N3O14P3 InChIKeyhelp_outline PCDQPRRSZKQHHS-XVFCMESISA-J SMILEShelp_outline Nc1ccn([C@@H]2O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]2O)c(=O)n1 2D coordinates Mol file for the small molecule Search links Involved in 78 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline D-ribose 5-phosphate Identifier CHEBI:78346 Charge -2 Formula C5H9O8P InChIKeyhelp_outline KTVPXOYAKDPRHY-SOOFDHNKSA-L SMILEShelp_outline OC1O[C@H](COP([O-])([O-])=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 25 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline CDP-D-ribose Identifier CHEBI:137525 Charge -2 Formula C14H21N3O15P2 InChIKeyhelp_outline FCHBMOTWOURDNP-HRENORGGSA-L SMILEShelp_outline O(P(OP(OC[C@H]([C@H]([C@H](C([H])=O)O)O)O)(=O)[O-])(=O)[O-])C[C@H]1O[C@H]([C@@H]([C@@H]1O)O)N2C(N=C(C=C2)N)=O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline diphosphate Identifier CHEBI:33019 (Beilstein: 185088) help_outline Charge -3 Formula HO7P2 InChIKeyhelp_outline XPPKVPWEQAFLFU-UHFFFAOYSA-K SMILEShelp_outline OP([O-])(=O)OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 1,085 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:53872 | RHEA:53873 | RHEA:53874 | RHEA:53875 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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The functional O-mannose glycan on alpha-dystroglycan contains a phospho-ribitol primed for matriglycan addition.
Praissman J.L., Willer T., Sheikh M.O., Toi A., Chitayat D., Lin Y.Y., Lee H., Stalnaker S.H., Wang S., Prabhakar P.K., Nelson S.F., Stemple D.L., Moore S.A., Moremen K.W., Campbell K.P., Wells L.
Multiple glycosyltransferases are essential for the proper modification of alpha-dystroglycan, as mutations in the encoding genes cause congenital/limb-girdle muscular dystrophies. Here we elucidate further the structure of an O-mannose-initiated glycan on alpha-dystroglycan that is required to ge ... >> More
Multiple glycosyltransferases are essential for the proper modification of alpha-dystroglycan, as mutations in the encoding genes cause congenital/limb-girdle muscular dystrophies. Here we elucidate further the structure of an O-mannose-initiated glycan on alpha-dystroglycan that is required to generate its extracellular matrix-binding polysaccharide. This functional glycan contains a novel ribitol structure that links a phosphotrisaccharide to xylose. ISPD is a CDP-ribitol (ribose) pyrophosphorylase that generates the reduced sugar nucleotide for the insertion of ribitol in a phosphodiester linkage to the glycoprotein. TMEM5 is a UDP-xylosyl transferase that elaborates the structure. We demonstrate in a zebrafish model as well as in a human patient that defects in TMEM5 result in muscular dystrophy in combination with abnormal brain development. Thus, we propose a novel structure-a ribitol in a phosphodiester linkage-for the moiety on which TMEM5, B4GAT1, and LARGE act to generate the functional receptor for ECM proteins having LG domains. << Less
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Human ISPD is a cytidyltransferase required for dystroglycan O-mannosylation.
Riemersma M., Froese D.S., van Tol W., Engelke U.F., Kopec J., van Scherpenzeel M., Ashikov A., Krojer T., von Delft F., Tessari M., Buczkowska A., Swiezewska E., Jae L.T., Brummelkamp T.R., Manya H., Endo T., van Bokhoven H., Yue W.W., Lefeber D.J.
A unique, unsolved O-mannosyl glycan on α-dystroglycan is essential for its interaction with protein ligands in the extracellular matrix. Defective O-mannosylation leads to a group of muscular dystrophies, called dystroglycanopathies. Mutations in isoprenoid synthase domain containing (ISPD) repre ... >> More
A unique, unsolved O-mannosyl glycan on α-dystroglycan is essential for its interaction with protein ligands in the extracellular matrix. Defective O-mannosylation leads to a group of muscular dystrophies, called dystroglycanopathies. Mutations in isoprenoid synthase domain containing (ISPD) represent the second most common cause of these disorders, however, its molecular function remains uncharacterized. The human ISPD (hISPD) crystal structure showed a canonical N-terminal cytidyltransferase domain linked to a C-terminal domain that is absent in cytidyltransferase homologs. Functional studies demonstrated cytosolic localization of hISPD, and cytidyltransferase activity toward pentose phosphates, including ribulose 5-phosphate, ribose 5-phosphate, and ribitol 5-phosphate. Identity of the CDP sugars was confirmed by liquid chromatography quadrupole time-of-flight mass spectrometry and two-dimensional nuclear magnetic resonance spectroscopy. Our combined results indicate that hISPD is a cytidyltransferase, suggesting the presence of a novel human nucleotide sugar essential for functional α-dystroglycan O-mannosylation in muscle and brain. Thereby, ISPD deficiency can be added to the growing list of tertiary dystroglycanopathies. << Less
Chem. Biol. 22:1643-1652(2015) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.