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Taxonomic group: protista / Euglenozoa (Phylum: Euglenozoa)
Host organism: (mammal)
Organ / tissue: Life stage: bloodstream form
Associated disease: infection due to Trypanosoma brucei [ICD11: XN0C1

]

The structure was elucidated in this paper
NCBI PubMed ID: 19919534
Publication DOI: 10.1042/BJ20090896
Journal NLM ID: 2984726R
Publisher: London, UK : Published by Portland Press on behalf of the Biochemical Society
Correspondence: tks1

st-andrews.ac.uk
Institutions: Biomolecular Sciences Research Complex, The North Haugh, The University, St Andrews, Fife KY16 9ST, Scotland, UK

A putative GDP-Man PP (guanidine diphosphomannose pyrophosphorylase) gene from Trypanosoma brucei (TbGDP-Man PP) was identified in the genome and subsequently cloned, sequenced and recombinantly expressed, and shown to be a catalytically active dimer. Kinetic analysis revealed a Vmax of 0.34 μmol/min per mg of protein and Km values of 67 μM and 12 μM for GTP and mannose 1-phosphate respectively. Further kinetic studies showed GDP-Man was a potent product feedback inhibitor. RNAi (RNA interference) of the cytosolic TbGDP-Man PP showed that mRNA levels were reduced to ~20% of wild-type levels, causing the cells to die after 3-4 days, demonstrating that TbGDP-Man PP is essential in the bloodstream form of T. brucei and thus a potential drug target. The RNAi-induced parasites have a greatly reduced capability to form GDP-Man, leading ultimately to a reduction in their ability to synthesize their essential GPI (glycosylphosphatidylinositol) anchors. The RNAi-induced parasites also showed aberrant N-glycosylation of their major cell-surface glycoprotein, variant surface glycoprotein, with loss of the high-mannose Man9GlcNAc2 N-glycosylation at Asn428 and formation of complex N-glycans at Asn263.

Glycosylphosphatidylinositol, N-glycosylation, Trypanosoma brucei, variant surface glycoprotein, essentiality, guanidine diphosphomannose pyrophosphorylase

Structure type: oligomer ; 956 [M+2H]2+
Location inside paper: p.612, GPI(Gal)5
Trivial name: sVSG, soluble-form VSG
Compound class: GPI-anchor VSG
Contained glycoepitopes: IEDB_120354,IEDB_123890,IEDB_130701,IEDB_131186,IEDB_134624,IEDB_135818,IEDB_136104,IEDB_136906,IEDB_137472,IEDB_140116,IEDB_140425,IEDB_140426,IEDB_141793,IEDB_141794,IEDB_141807,IEDB_141829,IEDB_142346,IEDB_142347,IEDB_142348,IEDB_143632,IEDB_144983,IEDB_144993,IEDB_145015,IEDB_150900,IEDB_151528,IEDB_151531,IEDB_152206,IEDB_153220,IEDB_190606,IEDB_474450,IEDB_983930,SB_136,SB_163,SB_191,SB_196,SB_198,SB_44,SB_67,SB_7,SB_72

Methods: gel filtration, ESI-MS, ESI-MS/MS, genetic methods, HPLC, enzymatic digestion, Southern blotting, RT-PCR, HPTLC, cloning, enzymatic assay

Related record ID(s): 4869, 4870, 4871, 4872, 4873, 4874, 4875, 4876, 4877, 7287
NCBI Taxonomy refs (TaxIDs): 5691
Show glycosyltransferases

There is only one chemically distinct structure:

NC(CO)C(=O)NCCOP(=O)(O)OC[C@H]1O[C@H](O[C@@H]2[C@@H](OC[C@H]3O[C@H](O[C@@H]4[C@@H](CO)O[C@H](O[C@@H]5[C@H]6OP(=O)(O)O[C@H]6[C@@H](O)[C@H](O)[C@H]5O)[C@H](N)[C@H]4O)[C@@H](O)[C@@H](O[C@H]4O[C@H](CO[C@H]5O[C@H](CO)[C@H](O)[C@H](O)[C@H]5O[C@H]5O[C@H](CO)[C@H](O)[C@H](O)[C@H]5O)[C@H](O)[C@H](O)[C@H]4O[C@H]4O[C@H](CO)[C@H](O)[C@H](O)[C@H]4O)[C@@H]3O)O[C@H](CO)[C@@H](O)[C@@H]2O)[C@@H](O[C@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)[C@@H](O)[C@@H]1O

SVG MW SMILES 3D mol Ionize