HPRK_LACCA
ID HPRK_LACCA Reviewed; 319 AA.
AC Q9RE09;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 109.
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 Lactobacillus casei.
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Lactobacillaceae;
OC Lacticaseibacillus.
OX NCBI_TaxID=1582;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CHARACTERIZATION.
RC STRAIN=ATCC 393 / DSM 20011 / BCRC 10697 / JCM 1134 / NBRC 15883 / NCIMB
RC 11970 / NCDO 161 / WDCM 00100;
RX PubMed=10762262; DOI=10.1128/jb.182.9.2582-2590.2000;
RA Dossonnet V., Monedero V., Zagorec M., Galinier A., Perez-Martinez G.,
RA Deutscher J.;
RT "Phosphorylation of HPr by the bifunctional HPr kinase/P-Ser-HPr
RT phosphatase from Lactobacillus casei controls catabolite repression and
RT inducer exclusion but not inducer expulsion.";
RL J. Bacteriol. 182:2582-2590(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 SUBUNIT, AND X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 135-307 IN COMPLEX
RP WITH PHOSPHATE.
RX PubMed=11483495; DOI=10.1093/emboj/20.15.3917;
RA Fieulaine S., Morera S., Poncet S., Monedero V., Gueguen-Chaignon V.,
RA Galinier A., Janin J., Deutscher J., Nessler S.;
RT "X-ray structure of HPr kinase: a bacterial protein kinase with a P-loop
RT nucleotide-binding domain.";
RL EMBO J. 20:3917-3927(2001).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 128-319 IN COMPLEXES WITH
RP B.SUBTILIS HPR AND B.SUBTILIS P-SER-HPR.
RX PubMed=12359875; DOI=10.1073/pnas.192368699;
RA Fieulaine S., Morera S., Poncet S., Mijakovic I., Galinier A., Janin J.,
RA Deutscher J., Nessler S.;
RT "X-ray structure of a bifunctional protein kinase in complex with its
RT protein substrate HPr.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13437-13441(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,
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;
CC -!- ACTIVITY REGULATION: Kinase activity is slightly activated by fructose
CC 1,6-bisphosphate (FBP), and inhibited by inorganic phosphate (Pi), but
CC FBP prevents kinase inhibition by Pi. Dephosphorylation of P-Ser-HPr is
CC slightly inhibited by FBP.
CC -!- SUBUNIT: Homohexamer, arranged as bilayered trimers. Six HPr molecules
CC bind to the hexamer at sites that overlap two of its subunits.
CC {ECO:0000269|PubMed:11483495}.
CC -!- DOMAIN: The Walker A ATP-binding motif also binds Pi and PPi.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: The truncated form that consists of amino acids 128-319
CC exhibits in vitro enzymatic activities identical to those of the full-
CC length protein, and also forms a hexamer.
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. {ECO:0000305}.
CC -!- CAUTION: Was originally (PubMed:10762262) called HPr
CC 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:10762262,
CC ECO:0000305|PubMed:12359880}.
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DR EMBL; Y18948; CAB65151.1; -; Genomic_DNA.
DR RefSeq; WP_003564222.1; NZ_MPOP01000004.1.
DR PDB; 1JB1; X-ray; 2.80 A; A=128-319.
DR PDB; 1KKL; X-ray; 2.80 A; A/B/C=128-319.
DR PDB; 1KKM; X-ray; 2.80 A; A/B/C=128-319.
DR PDB; 2QMH; X-ray; 2.60 A; A/B/C/D/E/F/G/H/I/J/K/L=128-319.
DR PDBsum; 1JB1; -.
DR PDBsum; 1KKL; -.
DR PDBsum; 1KKM; -.
DR PDBsum; 2QMH; -.
DR AlphaFoldDB; Q9RE09; -.
DR SMR; Q9RE09; -.
DR IntAct; Q9RE09; 1.
DR STRING; 1582.AAW28_02550; -.
DR GeneID; 61269162; -.
DR PATRIC; fig|1582.47.peg.1266; -.
DR eggNOG; COG1493; Bacteria.
DR OMA; AMNNRQK; -.
DR EvolutionaryTrace; Q9RE09; -.
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..319
FT /note="HPr kinase/phosphorylase"
FT /id="PRO_0000058959"
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"
FT ACT_SITE 140
FT ACT_SITE 161
FT ACT_SITE 179
FT /note="Proton acceptor; for phosphorylation activity.
FT Proton donor; for dephosphorylation activity"
FT ACT_SITE 245
FT BINDING 155..162
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT BINDING 162
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000305"
FT BINDING 204
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000305"
FT STRAND 139..146
FT /evidence="ECO:0007829|PDB:2QMH"
FT STRAND 149..154
FT /evidence="ECO:0007829|PDB:2QMH"
FT TURN 158..161
FT /evidence="ECO:0007829|PDB:2QMH"
FT HELIX 162..169
FT /evidence="ECO:0007829|PDB:2QMH"
FT TURN 170..172
FT /evidence="ECO:0007829|PDB:2QMH"
FT STRAND 174..185
FT /evidence="ECO:0007829|PDB:2QMH"
FT STRAND 187..189
FT /evidence="ECO:0007829|PDB:1JB1"
FT STRAND 191..194
FT /evidence="ECO:0007829|PDB:2QMH"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:2QMH"
FT STRAND 202..205
FT /evidence="ECO:0007829|PDB:2QMH"
FT TURN 206..208
FT /evidence="ECO:0007829|PDB:2QMH"
FT STRAND 209..212
FT /evidence="ECO:0007829|PDB:2QMH"
FT HELIX 213..217
FT /evidence="ECO:0007829|PDB:2QMH"
FT HELIX 219..221
FT /evidence="ECO:0007829|PDB:1JB1"
FT STRAND 224..227
FT /evidence="ECO:0007829|PDB:1JB1"
FT STRAND 230..234
FT /evidence="ECO:0007829|PDB:2QMH"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:2QMH"
FT STRAND 250..257
FT /evidence="ECO:0007829|PDB:2QMH"
FT STRAND 259..265
FT /evidence="ECO:0007829|PDB:2QMH"
FT HELIX 273..287
FT /evidence="ECO:0007829|PDB:2QMH"
FT TURN 288..290
FT /evidence="ECO:0007829|PDB:2QMH"
FT HELIX 293..306
FT /evidence="ECO:0007829|PDB:2QMH"
SQ SEQUENCE 319 AA; 35348 MW; 96D27AE3D31132E8 CRC64;
MADSVTVRQL VKATKLEVYS GEEYLDQRQV VLSDISRPGL ELTGYFNYYP HERIQLFGRT
EISFARNMSS EERLLILKRM ATEDTPAFLV SRGLEAPAEM ITAATAAHIP VLGSRLPTTR
LSSLITEYLD SQLAERRSMH GVLVDIYGLG VLITGDSGVG KSETALELVQ RGHRLIADDR
VDVYQQDEQT IVGAAPPILS HLLEIRGLGI IDVMNLFGAG AVREDTTISL IVHLENWTPD
KTFDRLGSGE QTQLIFDVPV PKITVPVKVG RNLAIIIEVA AMNFRAKSMG YDATKTFEKN
LNHLIEHNEE TDQNSSGDK
