Structural highlights
Function
[HPRK_LACCA] Catalyzes the ATP- as well as the pyrophosphate-dependent phosphorylation of 'Ser-46' in HPr, a phosphocarrier protein of the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS). HprK/P also catalyzes the pyrophosphate-producing, inorganic phosphate-dependent dephosphorylation (phosphorolysis) of seryl-phosphorylated HPr (P-Ser-HPr). The two antagonistic activities of HprK/P are regulated by several intracellular metabolites, which change their concentration in response to the absence or presence of rapidly metabolisable carbon sources (glucose, fructose, etc.) in the growth medium. Therefore, by controlling the phosphorylation state of HPr, HPrK/P is a sensor enzyme that plays a major role in the regulation of carbon metabolism and sugar transport: it mediates carbon catabolite repression (CCR), and regulates PTS-catalyzed carbohydrate uptake and inducer exclusion.[HAMAP-Rule:MF_01249]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
HPr kinase/phosphatase (HprK/P) is a key regulatory enzyme controlling carbon metabolism in Gram- positive bacteria. It catalyses the ATP-dependent phosphorylation of Ser46 in HPr, a protein of the phosphotransferase system, and also its dephosphorylation. HprK/P is unrelated to eukaryotic protein kinases, but contains the Walker motif A characteristic of nucleotide-binding proteins. We report here the X-ray structure of an active fragment of Lactobacillus casei HprK/P at 2.8 A resolution, solved by the multiwavelength anomalous dispersion method on a seleniated protein (PDB code 1jb1). The protein is a hexamer, with each subunit containing an ATP-binding domain similar to nucleoside/nucleotide kinases, and a putative HPr-binding domain unrelated to the substrate-binding domains of other kinases. The Walker motif A forms a typical P-loop which binds inorganic phosphate in the crystal. We modelled ATP binding by comparison with adenylate kinase, and designed a tentative model of the complex with HPr based on a docking simulation. The results confirm that HprK/P represents a new family of protein kinases, first identified in bacteria, but which may also have members in eukaryotes.
X-ray structure of HPr kinase: a bacterial protein kinase with a P-loop nucleotide-binding domain.,Fieulaine S, Morera S, Poncet S, Monedero V, Gueguen-Chaignon V, Galinier A, Janin J, Deutscher J, Nessler S EMBO J. 2001 Aug 1;20(15):3917-27. PMID:11483495[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fieulaine S, Morera S, Poncet S, Monedero V, Gueguen-Chaignon V, Galinier A, Janin J, Deutscher J, Nessler S. X-ray structure of HPr kinase: a bacterial protein kinase with a P-loop nucleotide-binding domain. EMBO J. 2001 Aug 1;20(15):3917-27. PMID:11483495 doi:10.1093/emboj/20.15.3917
