ArticleThe Journal of biological chemistry2013
Mycobacterium tuberculosis maltosyltransferase GlgE, a genetically validated antituberculosis target, is negatively regulated by Ser/Thr phosphorylation.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Architecture, Function, Regulation, and Evolution of α-Glucans Metabolic Enzymes in Prokaryotes.Chemical reviews · 2024Review
- Biochemical and structural characterization reveals Rv3400 codes for β-phosphoglucomutase in Mycobacterium tuberculosis.Protein science : a publication of the Protein Society · 2024Article
- A temperature-sensitive Mycobacterium smegmatis glgE mutation leads to a loss of GlgE enzyme activity and thermostability and the accumulation of α-maltose-1-phosphate.Biochimica et biophysica acta. General subjects · 2021Article
- Article
- Geochemical and metagenomics study of a metal-rich, green-turquoise-coloured stream in the southern Swiss Alps.PloS one · 2021Article
- TheThe Biochemical journal · 2019Review
- Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex.Scientific reports · 2019Article
- The serine/threonine kinase Stk and the phosphatase Stp regulate cell wall synthesis in Staphylococcus aureus.Scientific reports · 2018Article
- The Ser/Thr Protein Kinase Protein-Protein Interaction Map ofMolecular & cellular proteomics : MCP · 2017Article
- PknG senses amino acid availability to control metabolism and virulence of Mycobacterium tuberculosis.PLoS pathogens · 2017Article
- Epigenetic Phosphorylation Control of Mycobacterium tuberculosis Infection and Persistence.Microbiology spectrum · 2017Review
- Ligand-bound Structures and Site-directed Mutagenesis Identify the Acceptor and Secondary Binding Sites of Streptomyces coelicolor Maltosyltransferase GlgE.The Journal of biological chemistry · 2016Article
- Metabolic Network for the Biosynthesis of Intra- and Extracellular α-Glucans Required for Virulence of Mycobacterium tuberculosis.PLoS pathogens · 2016Article
- Developmental delay in a Streptomyces venezuelae glgE null mutant is associated with the accumulation of α-maltose 1-phosphate.Microbiology (Reading, England) · 2016Article
- Structure of Mycobacterium thermoresistibile GlgE defines novel conformational states that contribute to the catalytic mechanism.Scientific reports · 2015Article
- Regulation of Ergothioneine Biosynthesis and Its Effect on Mycobacterium tuberculosis Growth and Infectivity.The Journal of biological chemistry · 2015Article
- Allosteric regulation of the partitioning of glucose-1-phosphate between glycogen and trehalose biosynthesis in Mycobacterium tuberculosis.Biochimica et biophysica acta · 2015Article
- Phosphorylation of Mycobacterium tuberculosis ParB participates in regulating the ParABS chromosome segregation system.PloS one · 2015Article
- Mycobacterium tuberculosis Serine/Threonine Protein Kinases.Microbiology spectrum · 2014Review
- Structural insight into how Streptomyces coelicolor maltosyl transferase GlgE binds α-maltose 1-phosphate and forms a maltosyl-enzyme intermediate.Biochemistry · 2014Article
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
GlgE is a maltosyltransferase involved in the biosynthesis of α-glucans that has been genetically validated as a potential therapeutic target against Mycobacterium tuberculosis. Despite also making α-glucan, the GlgC/GlgA glycogen pathway is distinct and allosterically regulated. We have used a combination of genetics and biochemistry to establish how the GlgE pathway is regulated. M. tuberculosis GlgE was phosphorylated specifically by the Ser/Thr protein kinase PknB in vitro on one serine and six threonine residues. Furthermore, GlgE was phosphorylated in vivo when expressed in Mycobacterium bovis bacillus Calmette-Guérin (BCG) but not when all seven phosphorylation sites were replaced by Ala residues. The GlgE orthologues from Mycobacterium smegmatis and Streptomyces coelicolor were phosphorylated by the corresponding PknB orthologues in vitro, implying that the phosphorylation of GlgE is widespread among actinomycetes. PknB-dependent phosphorylation of GlgE led to a 2 orders of magnitude reduction in catalytic efficiency in vitro. The activities of phosphoablative and phosphomimetic GlgE derivatives, where each phosphorylation site was substituted with either Ala or Asp residues, respectively, correlated with negative phosphoregulation. Complementation studies of a M. smegmatis glgE mutant strain with these GlgE derivatives, together with both classical and chemical forward genetics, were consistent with flux through the GlgE pathway being correlated with GlgE activity. We conclude that the GlgE pathway appears to be negatively regulated in actinomycetes through the phosphorylation of GlgE by PknB, a mechanism distinct from that known in the classical glycogen pathway. Thus, these findings open new opportunities to target the GlgE pathway therapeutically.
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