HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Crh, the paralogue of the phosphocarrier protein HPr, controls the methylglyoxal bypass of glycolysis in Bacillus subtilis.

Abstract
The histidine protein HPr has a key role in regulation of carbohydrate utilization in low-GC Gram-positive bacteria. Bacilli possess the paralogue Crh. Like HPr, Crh becomes phosphorylated by kinase HPrK/P in response to high fructose-1,6-bisphosphate concentrations. However, Crh can only partially substitute for the regulatory functions of HPr leaving its role mysterious. Using protein co-purification, we identified enzyme methylglyoxal synthase MgsA as interaction partner of Crh in Bacillus subtilis. MgsA converts dihydroxyacetone-phosphate to methylglyoxal and thereby initiates a glycolytic bypass that prevents the deleterious accumulation of phospho-sugars under carbon overflow conditions. However, methylgyloxal is toxic and its production requires control. We show here that exclusively the non-phosphorylated form of Crh interacts with MgsA in vivo and inhibits MgsA activity in vitro. Accordingly, Crh inhibits methylglyoxal formation in vivo under nutritional famine conditions that favour a low HPr kinase activity. Thus, Crh senses the metabolic state of the cell, as reflected by its phosphorylation state, and accordingly controls flux through the harmful methylglyoxal pathway. Interestingly, HPr is unable to bind and regulate MgsA, making this a bona fide function of Crh. Four residues that differ in the interaction surfaces of HPr and Crh may account for this difference.
AuthorsJens J Landmann, Ricarda A Busse, Jan-Hendrik Latz, Kalpana D Singh, Jörg Stülke, Boris Görke
JournalMolecular microbiology (Mol Microbiol) Vol. 82 Issue 3 Pg. 770-87 (Nov 2011) ISSN: 1365-2958 [Electronic] England
PMID21992469 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2011 Blackwell Publishing Ltd.
Chemical References
  • Bacterial Proteins
  • Crh protein, Bacillus subtilis
  • Fructosediphosphates
  • Phosphoproteins
  • Dihydroxyacetone Phosphate
  • Pyruvaldehyde
  • Protein Kinases
  • fructose-1,6-diphosphate
Topics
  • Amino Acid Sequence
  • Bacillus subtilis (metabolism)
  • Bacterial Proteins (metabolism)
  • Dihydroxyacetone Phosphate (metabolism)
  • Fructosediphosphates (metabolism)
  • Glycolysis
  • Metabolic Networks and Pathways
  • Models, Biological
  • Molecular Sequence Data
  • Phosphoproteins (metabolism)
  • Phosphorylation
  • Protein Interaction Mapping
  • Protein Kinases (metabolism)
  • Pyruvaldehyde (metabolism)
  • Sequence Homology, Amino Acid

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: