AC MF_01249; DC Protein; auto TR HAMAP; MF_01249; -; 1; level=0 XX Names: HPr_kinase XX ID HPRK DE RecName: Full=HPr kinase/phosphorylase; DE Short=HPrK/P; DE EC=2.7.11.-; DE EC=2.7.4.-; DE AltName: Full=HPr(Ser) kinase/phosphorylase; GN Name=hprK; XX case CC -!- FUNCTION: Catalyzes the ATP- as well as the pyrophosphate-dependent CC phosphorylation of a specific serine residue in HPr, a phosphocarrier CC protein of the phosphoenolpyruvate-dependent sugar phosphotransferase CC system (PTS). HprK/P also catalyzes the pyrophosphate-producing, CC inorganic phosphate-dependent dephosphorylation (phosphorolysis) of CC seryl-phosphorylated HPr (P-Ser-HPr). The two antagonistic activities CC of HprK/P are regulated by several intracellular metabolites, which CC change their concentration in response to the absence or presence of CC rapidly metabolisable carbon sources (glucose, fructose, etc.) in the CC growth medium. Also phosphorylates/dephosphorylates the HPr-like CC catabolite repression protein crh on a specific serine residue. CC Therefore, by controlling the phosphorylation state of HPr and crh, CC HPrK/P is a sensor enzyme that plays a major role in the regulation of CC carbon metabolism and sugar transport: it mediates carbon catabolite CC repression (CCR), and regulates PTS-catalyzed carbohydrate uptake and CC inducer exclusion. end case case and not CC -!- FUNCTION: Catalyzes the ATP- as well as the pyrophosphate-dependent CC phosphorylation of a specific serine residue in HPr, a phosphocarrier CC protein of the phosphoenolpyruvate-dependent sugar phosphotransferase CC system (PTS). HprK/P also catalyzes the pyrophosphate-producing, CC inorganic phosphate-dependent dephosphorylation (phosphorolysis) of CC seryl-phosphorylated HPr (P-Ser-HPr). The two antagonistic activities CC of HprK/P are regulated by several intracellular metabolites, which CC change their concentration in response to the absence or presence of CC rapidly metabolisable carbon sources (glucose, fructose, etc.) in the CC growth medium. Therefore, by controlling the phosphorylation state of CC HPr, HPrK/P is a sensor enzyme that plays a major role in the CC regulation of carbon metabolism and sugar transport: it mediates carbon CC catabolite repression (CCR), and regulates PTS-catalyzed carbohydrate CC uptake and inducer exclusion. end case case not CC -!- FUNCTION: Catalyzes the ATP- as well as the pyrophosphate-dependent CC phosphorylation of a specific serine residue in HPr, a phosphocarrier CC protein of the phosphoenolpyruvate-dependent sugar phosphotransferase CC system (PTS). HprK/P also catalyzes the pyrophosphate-producing, CC inorganic phosphate-dependent dephosphorylation (phosphorolysis) of CC seryl-phosphorylated HPr (P-Ser-HPr). end case CC -!- CATALYTIC ACTIVITY: CC Reaction=[HPr protein]-L-serine + ATP = [HPr protein]-O-phospho-L- CC serine + ADP + H(+); Xref=Rhea:RHEA:46600, Rhea:RHEA-COMP:11602, CC Rhea:RHEA-COMP:11603, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; CC -!- CATALYTIC ACTIVITY: CC Reaction=[HPr protein]-O-phospho-L-serine + H(+) + phosphate = [HPr CC protein]-L-serine + diphosphate; Xref=Rhea:RHEA:46604, Rhea:RHEA- CC COMP:11602, Rhea:RHEA-COMP:11603, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:29999, ChEBI:CHEBI:33019, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:83421; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC -!- SUBUNIT: Homohexamer. CC -!- DOMAIN: The Walker A ATP-binding motif also binds Pi and PPi. CC -!- MISCELLANEOUS: Both phosphorylation and phosphorolysis are carried out CC by the same active site and suggest a common mechanism for both CC reactions. CC -!- SIMILARITY: Belongs to the HPrK/P family. XX DR Pfam; PF07475; Hpr_kinase_C; 1; trigger=no DR Pfam; PF02603; Hpr_kinase_N; 1; trigger=no DR NCBIfam; TIGR00679; Hpr-ser; 1; trigger=no XX KW Multifunctional enzyme KW Transferase KW Kinase KW Serine/threonine-protein kinase case KW Carbohydrate metabolism end case KW ATP-binding KW Nucleotide-binding KW Magnesium KW Metal-binding XX GO GO:0000287; F:magnesium ion binding GO GO:0004712; F:protein serine/threonine/tyrosine kinase activity GO GO:0005524; F:ATP binding GO GO:0006109; P:regulation of carbohydrate metabolic process XX FT From: HPRK_LACCA (Q9RE09) FT BINDING 155..162 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT Condition: G-x-[SA]-G-x-G-K-S FT ACT_SITE 140 FT Condition: H FT ACT_SITE 161 FT Condition: K FT ACT_SITE 179 FT /note="Proton acceptor; for phosphorylation activity. FT Proton donor; for dephosphorylation activity" FT Condition: D FT ACT_SITE 245 FT Condition: R FT BINDING 162 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT Condition: S FT BINDING 204 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT Condition: E FT REGION 203..212 FT /note="Important for the catalytic mechanism of both FT phosphorylation and dephosphorylation" FT REGION 266..271 FT /note="Important for the catalytic mechanism of FT dephosphorylation" XX Size: 301-342; Related: None; Template: O34483; Q9RE09; P75548; Q9S1H5; Q9WXK7; Q9ZA98; Scope: Bacteria Fusion: Nter: None Cter: None Duplicate: in OCEIH Plasmid: None Comments: This enzyme was originally called HPr kinase/phosphatase, but P-Ser-HPr dephosphorylation was recently found to follow a quite unique mechanism, in which Pi instead of H(2)O is used for the nucleophilic attack on the phosphoryl group. P-Ser-HPr dephosphorylation is therefore not a phosphohydrolysis but a phosphophosphorolysis reaction, and the bifunctional enzyme was dubbed HPr kinase/phosphorylase. The regulatory role(s) of HPrK/P in bacterial physiology may be quite diverse. In low GC Gram-positive bacteria, HPr kinase/phosphorylase plays a major role in the regulation of carbon metabolism as it is a bifunctional sensor enzyme for CCR, PTS-catalyzed sugar transport and inducer exclusion. But HPRK/P must carry out different regulatory functions in Gram-negative bacteria, as these bacteria are devoid of ccpA protein, and a functional PTS also seems to be absent. The gene organization in many hprK-containing Gram-negative bacteria strongly suggest that HPrK/P regulates either a two-component sensory system implicated in cell adhesion/virology or rpoN-like sigma-factors. In Fusobacterium nucleatum, this protein is composed of two complete HPrK/P domains fused in tandem. XX # Revision 1.28 2023/06/01 //