Structural basis for the broad substrate range of the UDP-sugar pyrophosphorylase from Leishmania major.

@article{Dickmanns2011StructuralBF,
  title={Structural basis for the broad substrate range of the UDP-sugar pyrophosphorylase from Leishmania major.},
  author={Achim Dickmanns and Sebastian Damerow and Piotr Neumann and Eike C. Schulz and Anne-Christin Lamerz and Françoise H. Routier and Ralf Ficner},
  journal={Journal of molecular biology},
  year={2011},
  volume={405 2},
  pages={
          461-78
        }
}
Nucleotide sugars and the enzymes that are responsible for their synthesis are indispensable for the production of complex carbohydrates and, thus, for elaboration of a protective cellular coat for many organisms such as the protozoan parasite Leishmania. These activated sugars are synthesized de novo or derived from salvaged monosaccharides. In addition to UDP-glucose (UDP-Glc) pyrophosphorylase, which catalyzes the formation of UDP-Glc from substrates UTP and glucose-1-phosphate, Leishmania… Expand
Substrate Specificity and Inhibitor Sensitivity of Plant UDP-Sugar Producing Pyrophosphorylases
TLDR
Homology models of UDP-sugar binding to UGPase, USPase and UAGPase2 revealed more common amino acids for UDP binding than for sugar binding, reflecting differences in substrate specificity of these proteins. Expand
Identification and characterization of inhibitors of UDP‐glucose and UDP‐sugar pyrophosphorylases for in vivo studies
TLDR
The results suggest that cmp #6 and its analogs may represent useful tools to study in vivo roles of the pyrophosphorylases, helping to overcome the limitations of genetic approaches. Expand
The UDP-glucose pyrophosphorylase from Giardia lamblia is redox regulated and exhibits promiscuity to use galactose-1-phosphate.
TLDR
The characterization of the G. lamblia UDP-glucose pyrophosphorylase reinforces the view that in protozoa this enzyme is regulated by a redox mechanism and proposes a new pathway for UDP-galactose production mediated by the promiscuous UDP- glucosepyrophosphorouslase of this organism. Expand
UDP-Sugar Producing Pyrophosphorylases: Distinct and Essential Enzymes With Overlapping Substrate Specificities, Providing de novo Precursors for Glycosylation Reactions
TLDR
Primary mechanisms of formation of UDP-sugars are covered, by focusing on UDP-Sugar metabolizing pyrophosphorylases, and substrate specificities of these enzymes are discussed, along with structure-function relationships, based on their crystal structures and homology modeling. Expand
Substrate kinetics and substrate effects on the quaternary structure of barley UDP-glucose pyrophosphorylase.
TLDR
The quaternary structure of the enzyme, studied by Gas-phase Electrophoretic Mobility Macromolecule Analysis (GEMMA), was affected by addition of either single or both substrates in either direction of the reaction, resulting in a shift from UGPase dimers toward monomers, the active form of the enzymes. Expand
Depletion of UDP-Glucose and UDP-Galactose Using a Degron System Leads to Growth Cessation of Leishmania major
TLDR
Under destabilising conditions, the absence of both UGP and USP resulted in depletion of UDP-Glc and UDP-Gal and led to growth cessation and cell death, suggesting that either or both of these metabolites is/are essential. Expand
Biosynthesis of GDP-fucose and Other Sugar Nucleotides in the Blood Stages of Plasmodium falciparum*
TLDR
The in silico functional reconstruction of the parasite metabolic pathways obtained from the P. falciparum annotated genome exposes new active biosynthetic routes crucial for further glycosylation reactions. Expand
Update on Nucleotide Sugar Synthesis UDP-Sugar Pyrophosphorylase: A New Old Mechanism for Sugar Activation
Simple sugars (e.g. Glc, Gal) are the building blocks of disaccharides (e.g. Suc) and polysaccharides (e.g. cellulose, hemicellulose). To produce disaccharides and polysaccharides, a given simpleExpand
GlmU (N-acetylglucosamine-1-phosphate uridyltransferase) bound to three magnesium ions and ATP at the active site.
TLDR
The enzymatic assays reported here demonstrate that GlmU is specific for its natural substrates UTP and GlcNAc-1-P, and the crystal structure provides molecular details for the inability of the enzyme to utilize ATP for the nucleotidyltransfer reaction. Expand
A common structural blueprint for plant UDP-sugar-producing pyrophosphorylases.
TLDR
Plant pyrophosphorylases that are capable of producing UDP-sugars, key precursors for glycosylation reactions, include UDP-glucose pyroph phosphorylase, which are characterized by the presence of the Rossmann fold in the central (catalytic) domain linked to enzyme-specific N- terminal and C-terminal domains, which may play regulatory functions. Expand
...
1
2
3
4
...

References

SHOWING 1-10 OF 68 REFERENCES
Leishmania UDP-sugar Pyrophosphorylase
TLDR
The characterization of an L. major UDP-sugar pyrophosphorylase able to reversibly activate galactose 1-phosphate into UDP-galactose is presented thus proving the existence of the Isselbacher salvage pathway in this parasite. Expand
UDP-sugar Pyrophosphorylase with Broad Substrate Specificity Toward Various Monosaccharide 1-Phosphates from Pea Sprouts*
TLDR
Recombinant PsUSP expressed in Escherichia coli catalyzed the formation of UDP-sugars from monosaccharide 1-phosphates and UTP with efficiency similar to that of the native enzyme. Expand
Identification of a novel UDP-sugar pyrophosphorylase with a broad substrate specificity in Trypanosoma cruzi.
TLDR
A functional gene from Trypanosoma cruzi is reported that encodes a nucleotidyltransferase, which is capable of transforming different types of sugar 1-phosphates and NTP into NDP-sugars, which suggests an alternative pathway that might play an essential role for nucleotide-sugar biosynthesis and for the regulation of the NDP-Sugar pool in the parasite. Expand
Structural basis for the reaction mechanism of UDP-glucose pyrophosphorylase
TLDR
Isothermal titration calorimetry analyses demonstrated that Mg2+ ion plays a key role in the enzymatic activity of UGPase by enhancing the binding of U GPase to UTP or UDP-glucose, suggesting that this reaction is catalyzed by an ordered sequential Bi Bi mechanism. Expand
Open and Closed Structures of the UDP-glucose Pyrophosphorylase from Leishmania major*
TLDR
The presented structures together with mutagenesis analyses provide a basis for a detailed analysis of the catalytic mechanism and for the design of species-specific UGPase inhibitors. Expand
Structural basis for subunit assembly in UDP-glucose pyrophosphorylase from Saccharomyces cerevisiae.
TLDR
The crystal structure of yeast UGPase, Ugp1p, is presented and conservation of hydrophobic residues at the subunit interfaces suggests that all fungal and animal homologs form this quarternary structure arrangement in contrast to monomeric plant UGPases, which have charged residues at these positions. Expand
Properties and Physiological Functions of UDP-Sugar Pyrophosphorylase in Arabidopsis
TLDR
Results indicate that AtUSP functions as a UDP-sugar pyrophosphorylase in the salvage pathway, and that the generation of UDP-Sugars from monosaccharide 1-phosphates catalyzed by AtUSp is essential for pollen development in Arabidopsis. Expand
Molecular Cloning of the Leishmania major UDP-glucose Pyrophosphorylase, Functional Characterization, and Ligand Binding Analyses Using NMR Spectroscopy*
TLDR
The identification of Leishmania major UDP-glucose pyrophosphorylase (UGP) is reported, providing the first direct proof for the ordered bi-bi mechanism suggested in earlier studies. Expand
Deletion of UDP-glucose pyrophosphorylase reveals a UDP-glucose independent UDP-galactose salvage pathway in Leishmania major.
TLDR
The data suggest that Leishmania elaborates a UDP-Glc independent salvage pathway for UDP-Gal biosynthesis, and that the virulence of the UGP-deficient mutant was only modestly affected. Expand
Crystal Structure of Uridine-diphospho-N-acetylglucosamine Pyrophosphorylase from Candida albicans and Catalytic Reaction Mechanism*
TLDR
A magnesium ion enhances the enzymatic activity of CaUAP1, and thus it is proposed that the magnesium ion increases the affinity between UTP and the enzyme by coordinating to the α- and γ-phosphate group of UTP. Expand
...
1
2
3
4
5
...