HPRK_STAXY
ID HPRK_STAXY Reviewed; 314 AA.
AC Q9S1H5;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=HPr kinase/phosphorylase;
DE Short=HPrK/P;
DE EC=2.7.11.-;
DE EC=2.7.4.-;
DE AltName: Full=HPr kinase/phosphatase;
DE AltName: Full=HPr(Ser) kinase/phosphorylase;
GN Name=hprK;
OS Staphylococcus xylosus.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=1288;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CHARACTERIZATION.
RC STRAIN=DSM 20267 / Isolate C2A;
RX PubMed=10714994; DOI=10.1128/jb.182.7.1895-1902.2000;
RA Huynh P.L., Jankovic I., Schnell N., Brueckner R.;
RT "Characterization of an HPr kinase mutant of Staphylococcus xylosus.";
RL J. Bacteriol. 182:1895-1902(2000).
RN [2]
RP DEPHOSPHORYLATION REACTION MECHANISM.
RX PubMed=12359880; DOI=10.1073/pnas.212410399;
RA Mijakovic I., Poncet S., Galinier A., Monedero V., Fieulaine S., Janin J.,
RA Nessler S., Marquez J.A., Scheffzek K., Hasenbein S., Hengstenberg W.,
RA Deutscher J.;
RT "Pyrophosphate-producing protein dephosphorylation by HPr
RT kinase/phosphorylase: a relic of early life?";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13442-13447(2002).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
RC STRAIN=DSM 20267 / Isolate C2A;
RX PubMed=11904409; DOI=10.1073/pnas.052461499;
RA Marquez J.A., Hasenbein S., Koch B., Fieulaine S., Nessler S.,
RA Russell R.B., Hengstenberg W., Scheffzek K.;
RT "Structure of the full-length HPr kinase/phosphatase from Staphylococcus
RT xylosus at 1.95 A resolution: mimicking the product/substrate of the
RT phospho transfer reactions.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:3458-3463(2002).
CC -!- FUNCTION: Catalyzes the ATP- as well as the pyrophosphate-dependent
CC phosphorylation of 'Ser-46' in HPr, a phosphocarrier protein of the
CC phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS).
CC HprK/P also catalyzes the pyrophosphate-producing, inorganic phosphate-
CC dependent dephosphorylation (phosphorolysis) of seryl-phosphorylated
CC HPr (P-Ser-HPr). The two antagonistic activities of HprK/P are
CC regulated by several intracellular metabolites, which change their
CC concentration in response to the absence or presence of rapidly
CC metabolisable carbon sources (glucose, fructose, etc.) in the growth
CC medium. Therefore, by controlling the phosphorylation state of HPr, the
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.
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; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Kinase activity is activated by fructose 1,6-
CC bisphosphate (FBP) only at low concentrations of enzyme or at high ATP
CC concentrations.
CC -!- SUBUNIT: Homohexamer, arranged as bilayered trimers.
CC -!- INDUCTION: Constitutively expressed, with or without glucose in the
CC growth medium.
CC -!- DOMAIN: The Walker A ATP-binding motif also binds Pi and PPi.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: Both phosphorylation and phosphorolysis are carried out
CC by the same active site and suggest a common mechanism for both
CC reactions. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the HPrK/P family. {ECO:0000305}.
CC -!- CAUTION: Was originally (PubMed:10714994 and PubMed:11904409) called
CC HPr kinase/phosphatase, but P-Ser-HPr dephosphorylation was shown
CC (PubMed:12359880) to follow a quite unique mechanism, in which Pi
CC instead of H(2)O is used for the nucleophilic attack on the phosphoryl
CC group. P-Ser-HPr dephosphorylation is therefore not a phosphohydrolysis
CC but a phospho-phosphorolysis reaction, and the bifunctional enzyme was
CC dubbed HPr kinase/phosphorylase. {ECO:0000305|PubMed:12359880}.
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DR EMBL; AJ243915; CAB51944.1; -; Genomic_DNA.
DR RefSeq; WP_042363085.1; NZ_VBTJ01000001.1.
DR PDB; 1KO7; X-ray; 1.95 A; A/B=1-314.
DR PDBsum; 1KO7; -.
DR AlphaFoldDB; Q9S1H5; -.
DR SMR; Q9S1H5; -.
DR STRING; 1288.SXYLSMQ121_1936; -.
DR GeneID; 45497584; -.
DR eggNOG; COG1493; Bacteria.
DR OrthoDB; 391150at2; -.
DR EvolutionaryTrace; Q9S1H5; -.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0000155; F:phosphorelay sensor kinase activity; IEA:InterPro.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006109; P:regulation of carbohydrate metabolic process; IEA:UniProtKB-UniRule.
DR CDD; cd01918; HprK_C; 1.
DR Gene3D; 3.40.1390.20; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_01249; HPr_kinase; 1.
DR InterPro; IPR003755; HPr(Ser)_kin/Pase.
DR InterPro; IPR011104; Hpr_kin/Pase_C.
DR InterPro; IPR011126; Hpr_kin/Pase_Hpr_N.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR028979; Ser_kin/Pase_Hpr-like_N_sf.
DR PANTHER; PTHR30305:SF1; PTHR30305:SF1; 1.
DR Pfam; PF07475; Hpr_kinase_C; 1.
DR Pfam; PF02603; Hpr_kinase_N; 1.
DR SUPFAM; SSF75138; SSF75138; 1.
DR TIGRFAMs; TIGR00679; hpr-ser; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Carbohydrate metabolism; Kinase; Magnesium;
KW Metal-binding; Multifunctional enzyme; Nucleotide-binding;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..314
FT /note="HPr kinase/phosphorylase"
FT /id="PRO_0000058991"
FT REGION 199..208
FT /note="Important for the catalytic mechanism of both
FT phosphorylation and dephosphorylation"
FT /evidence="ECO:0000250"
FT REGION 262..267
FT /note="Important for the catalytic mechanism of
FT dephosphorylation"
FT /evidence="ECO:0000250"
FT ACT_SITE 136
FT /evidence="ECO:0000250"
FT ACT_SITE 157
FT /evidence="ECO:0000250"
FT ACT_SITE 175
FT /note="Proton acceptor; for phosphorylation activity.
FT Proton donor; for dephosphorylation activity"
FT /evidence="ECO:0000250"
FT ACT_SITE 241
FT /evidence="ECO:0000250"
FT BINDING 151..158
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT BINDING 158
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255"
FT BINDING 200
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255"
FT HELIX 4..11
FT /evidence="ECO:0007829|PDB:1KO7"
FT STRAND 14..17
FT /evidence="ECO:0007829|PDB:1KO7"
FT HELIX 19..21
FT /evidence="ECO:0007829|PDB:1KO7"
FT HELIX 35..38
FT /evidence="ECO:0007829|PDB:1KO7"
FT STRAND 49..53
FT /evidence="ECO:0007829|PDB:1KO7"
FT HELIX 55..63
FT /evidence="ECO:0007829|PDB:1KO7"
FT HELIX 66..69
FT /evidence="ECO:0007829|PDB:1KO7"
FT HELIX 72..76
FT /evidence="ECO:0007829|PDB:1KO7"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:1KO7"
FT HELIX 94..102
FT /evidence="ECO:0007829|PDB:1KO7"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:1KO7"
FT HELIX 114..128
FT /evidence="ECO:0007829|PDB:1KO7"
FT STRAND 131..142
FT /evidence="ECO:0007829|PDB:1KO7"
FT STRAND 145..152
FT /evidence="ECO:0007829|PDB:1KO7"
FT HELIX 157..166
FT /evidence="ECO:0007829|PDB:1KO7"
FT STRAND 170..185
FT /evidence="ECO:0007829|PDB:1KO7"
FT STRAND 187..190
FT /evidence="ECO:0007829|PDB:1KO7"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:1KO7"
FT STRAND 198..201
FT /evidence="ECO:0007829|PDB:1KO7"
FT TURN 202..204
FT /evidence="ECO:0007829|PDB:1KO7"
FT STRAND 205..208
FT /evidence="ECO:0007829|PDB:1KO7"
FT HELIX 209..213
FT /evidence="ECO:0007829|PDB:1KO7"
FT HELIX 215..217
FT /evidence="ECO:0007829|PDB:1KO7"
FT STRAND 220..223
FT /evidence="ECO:0007829|PDB:1KO7"
FT STRAND 226..231
FT /evidence="ECO:0007829|PDB:1KO7"
FT STRAND 247..251
FT /evidence="ECO:0007829|PDB:1KO7"
FT STRAND 254..262
FT /evidence="ECO:0007829|PDB:1KO7"
FT HELIX 269..284
FT /evidence="ECO:0007829|PDB:1KO7"
FT HELIX 289..297
FT /evidence="ECO:0007829|PDB:1KO7"
SQ SEQUENCE 314 AA; 35325 MW; 04B5CBDD4DC4BD45 CRC64;
MLTTKSLVER FELEMIAGEA GLNKQIKNTD ISRPGLEMAG YFSHYASDRI QLLGTTELSF
YNLLPDEERK GRMRKLCRPE TPAIIVTRDL EPPEELIEAA KEHETPLITS KIATTQLMSR
LTTFLEHELA RTTSLHGVLV DVYGVGVLIT GDSGIGKSET ALELIKRGHR LVADDNVEIR
EISKDELIGR APKLIEHLLE IRGLGIINVM TLFGAGSILT EKRLRLNIHL ENWHKEKLYD
RVGLNEETLR ILDTEITKKT IPVRPGRNVA VIIEVAAMNY RLNIMGINTA EEFNDRLNAE
ILRNGNNGNN GEEK
