ID   HPRK_MYCPN              Reviewed;         312 AA.
AC   P75548;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1997, sequence version 1.
DT   29-MAY-2024, entry version 144.
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; Synonyms=ptsK; OrderedLocusNames=MPN_223; ORFNames=MP608;
OS   Mycoplasma pneumoniae (strain ATCC 29342 / M129 / Subtype 1)
OS   (Mycoplasmoides pneumoniae).
OC   Bacteria; Mycoplasmatota; Mycoplasmoidales; Mycoplasmoidaceae;
OC   Mycoplasmoides.
OX   NCBI_TaxID=272634;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 29342 / M129 / Subtype 1;
RX   PubMed=8948633; DOI=10.1093/nar/24.22.4420;
RA   Himmelreich R., Hilbert H., Plagens H., Pirkl E., Li B.-C., Herrmann R.;
RT   "Complete sequence analysis of the genome of the bacterium Mycoplasma
RT   pneumoniae.";
RL   Nucleic Acids Res. 24:4420-4449(1996).
RN   [2]
RP   CHARACTERIZATION, AND MUTAGENESIS OF RESIDUES IN THE WALKER MOTIF A AND IN
RP   THE HPRK/P SIGNATURE SEQUENCE.
RX   PubMed=12368461; DOI=10.1099/00221287-148-10-3277;
RA   Steinhauer K., Jepp T., Hillen W., Stuelke J.;
RT   "A novel mode of control of Mycoplasma pneumoniae HPr kinase/phosphatase
RT   activity reflects its parasitic lifestyle.";
RL   Microbiology 148:3277-3284(2002).
RN   [3]
RP   CHARACTERIZATION, AND MUTAGENESIS OF GLY-154; GLY-159; LYS-160; SER-161;
RP   ARG-204 AND GLY-207.
RX   PubMed=14717704; DOI=10.1046/j.1432-1033.2003.03935.x;
RA   Merzbacher M., Detsch C., Hillen W., Stuelke J.;
RT   "Mycoplasma pneumoniae HPr kinase/phosphorylase.";
RL   Eur. J. Biochem. 271:367-374(2004).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX   PubMed=12589763; DOI=10.1016/s0022-2836(02)01378-5;
RA   Allen G.S., Steinhauer K., Hillen W., Stuelke J., Brennan R.G.;
RT   "Crystal structure of HPr kinase/phosphatase from Mycoplasma pneumoniae.";
RL   J. Mol. Biol. 326:1203-1217(2003).
CC   -!- FUNCTION: Is a metabolite-sensitive enzyme that catalyzes the ATP-as
CC       well as probably the pyrophosphate-dependent phosphorylation of Ser-47
CC       in HPr, a phosphocarrier protein of the phosphoenolpyruvate-dependent
CC       sugar phosphotransferase system (PTS). HprK/P also catalyzes the
CC       pyrophosphate-producing, inorganic phosphate-dependent
CC       dephosphorylation (phosphorolysis) of seryl-phosphorylated HPr (P-Ser-
CC       HPr). The regulatory role of HPrK/P in the physiology of M.pneumoniae
CC       is not known yet.
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: Contrary to HPrK/P of B.subtilis and other
CC       bacteria, that of M.pneumoniae is active as a kinase at very low ATP
CC       concentrations in the absence of fructose 1,6-bisphosphate (FBP).
CC       Kinase activity is slightly activated by FBP, and inhibited by
CC       inorganic phosphate (Pi), but FBP prevents kinase inhibition by Pi.
CC       Dephosphorylation of P-Ser-HPr by M.pneumoniae HPrK/P is strictly
CC       dependent on the presence of Pi, and is inhibited by FBP. This unique
CC       mode of control of HPrK/P activity is proposed to reflect the parasitic
CC       lifestyle of M.pneumoniae, that is strictly adapted to its ecological
CC       niche on nutrient-rich human mucous membranes.
CC   -!- SUBUNIT: Homohexamer, arranged as bilayered trimers.
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   -!- MISCELLANEOUS: Contrary to HPrK/P of other bacteria, that of
CC       M.pneumoniae has a very high affinity for ATP (Kd=5.3 microM),
CC       explaining kinase activity even at low ATP concentrations.
CC   -!- SIMILARITY: Belongs to the HPrK/P family. {ECO:0000305}.
CC   -!- CAUTION: Was originally called HPr kinase/phosphatase (PubMed:12368461,
CC       PubMed:12589763). But P-Ser-HPr dephosphorylation was shown in several
CC       bacteria to follow a quite unique mechanism, in which Pi instead of
CC       H(2)O is used for the nucleophilic attack on the phosphoryl group. P-
CC       Ser-HPr dephosphorylation is therefore not a phosphohydrolysis but a
CC       phospho-phosphorolysis reaction, and the bifunctional enzyme was dubbed
CC       HPr kinase/phosphorylase. {ECO:0000305}.
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DR   EMBL; U00089; AAB96256.1; -; Genomic_DNA.
DR   PIR; S73934; S73934.
DR   RefSeq; NP_109911.1; NC_000912.1.
DR   RefSeq; WP_010874580.1; NZ_OU342337.1.
DR   PDB; 1KNX; X-ray; 2.50 A; A/B/C/D/E/F=1-312.
DR   PDBsum; 1KNX; -.
DR   AlphaFoldDB; P75548; -.
DR   SMR; P75548; -.
DR   IntAct; P75548; 4.
DR   STRING; 272634.MPN_223; -.
DR   EnsemblBacteria; AAB96256; AAB96256; MPN_223.
DR   GeneID; 66609131; -.
DR   KEGG; mpn:MPN_223; -.
DR   PATRIC; fig|272634.6.peg.242; -.
DR   HOGENOM; CLU_052030_0_1_14; -.
DR   OrthoDB; 9778803at2; -.
DR   BioCyc; MPNE272634:G1GJ3-358-MONOMER; -.
DR   EvolutionaryTrace; P75548; -.
DR   Proteomes; UP000000808; Chromosome.
DR   GO; GO:0005829; C:cytosol; IEA:TreeGrafter.
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:0006109; P:regulation of carbohydrate metabolic process; IEA:UniProtKB-UniRule.
DR   CDD; cd01918; HprK_C; 1.
DR   Gene3D; 3.40.1390.20; HprK N-terminal domain-like; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 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   NCBIfam; TIGR00679; hpr-ser; 1.
DR   PANTHER; PTHR30305:SF1; HPR KINASE_PHOSPHORYLASE; 1.
DR   PANTHER; PTHR30305; UNCHARACTERIZED; 1.
DR   Pfam; PF07475; Hpr_kinase_C; 1.
DR   Pfam; PF02603; Hpr_kinase_N; 1.
DR   SUPFAM; SSF75138; HprK N-terminal domain-like; 1.
DR   SUPFAM; SSF53795; PEP carboxykinase-like; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Carbohydrate metabolism; Kinase; Magnesium;
KW   Metal-binding; Multifunctional enzyme; Nucleotide-binding;
KW   Reference proteome; Serine/threonine-protein kinase; Transferase.
FT   CHAIN           1..312
FT                   /note="HPr kinase/phosphorylase"
FT                   /id="PRO_0000058973"
FT   REGION          201..210
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                   /evidence="ECO:0000250"
FT   ACT_SITE        139
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        160
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        178
FT                   /note="Proton acceptor; for phosphorylation activity.
FT                   Proton donor; for dephosphorylation activity"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        245
FT                   /evidence="ECO:0000250"
FT   BINDING         154..161
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000305"
FT   BINDING         161
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000305"
FT   BINDING         202
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255"
FT   MUTAGEN         140
FT                   /note="G->A: Kinase activity not affected and 6-fold
FT                   increase in phosphorylase activity."
FT                   /evidence="ECO:0000269|PubMed:12368461"
FT   MUTAGEN         154
FT                   /note="G->A: 4-fold reduction in kinase activity and loss
FT                   of phosphorylase activity; 8-fold reduction in ATP
FT                   affinity."
FT                   /evidence="ECO:0000269|PubMed:14717704"
FT   MUTAGEN         156
FT                   /note="S->A: Kinase activity not affected and 4-fold
FT                   increase in phosphorylase activity."
FT                   /evidence="ECO:0000269|PubMed:12368461"
FT   MUTAGEN         156
FT                   /note="S->T: 4-fold reduction in kinase activity and loss
FT                   of phosphorylase activity."
FT                   /evidence="ECO:0000269|PubMed:12368461"
FT   MUTAGEN         157
FT                   /note="G->A: 4-fold reduction in kinase activity and
FT                   strongly reduced phosphorylase activity."
FT                   /evidence="ECO:0000269|PubMed:12368461"
FT   MUTAGEN         159
FT                   /note="G->A: Loss of both kinase and phosphorylase
FT                   activities; no ATP binding."
FT                   /evidence="ECO:0000269|PubMed:14717704"
FT   MUTAGEN         160
FT                   /note="K->A: Loss of both kinase and phosphorylase
FT                   activities; no ATP binding."
FT                   /evidence="ECO:0000269|PubMed:14717704"
FT   MUTAGEN         160
FT                   /note="K->R: Loss of both kinase and phosphorylase
FT                   activities."
FT                   /evidence="ECO:0000269|PubMed:14717704"
FT   MUTAGEN         161
FT                   /note="S->A: 10-fold reduction in kinase activity and loss
FT                   of phosphorylase activity; affinity for ATP is only
FT                   slightly affected."
FT                   /evidence="ECO:0000269|PubMed:14717704"
FT   MUTAGEN         161
FT                   /note="S->T: 2-fold reduction in kinase activity and
FT                   strongly reduced phosphorylase activity; binds ATP with
FT                   high affinity."
FT                   /evidence="ECO:0000269|PubMed:14717704"
FT   MUTAGEN         162
FT                   /note="E->D: Kinase activity not affected and loss of
FT                   phosphorylase activity."
FT                   /evidence="ECO:0000269|PubMed:12368461"
FT   MUTAGEN         204
FT                   /note="R->K: Kinase activity not affected and strongly
FT                   reduced phosphorylase activity; ATP binding not affected."
FT                   /evidence="ECO:0000269|PubMed:14717704"
FT   MUTAGEN         207
FT                   /note="G->A: Loss of both kinase and phosphorylase
FT                   activities; ATP binding not affected."
FT                   /evidence="ECO:0000269|PubMed:14717704"
FT   HELIX           6..10
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   TURN            14..16
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   HELIX           39..42
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   STRAND          54..56
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   HELIX           58..64
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   HELIX           69..72
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   TURN            73..75
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   HELIX           76..80
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   STRAND          87..90
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   TURN            91..93
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   HELIX           97..102
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   HELIX           103..105
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   STRAND          110..115
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   HELIX           117..120
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   TURN            121..123
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   HELIX           124..131
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   STRAND          136..145
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   STRAND          148..159
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   HELIX           160..168
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   TURN            169..171
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   STRAND          173..185
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   STRAND          188..193
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   TURN            195..199
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   STRAND          200..203
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   TURN            204..206
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   STRAND          207..210
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   HELIX           211..215
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   HELIX           217..219
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   STRAND          224..233
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   STRAND          252..255
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   STRAND          258..266
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   HELIX           273..288
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   HELIX           293..304
FT                   /evidence="ECO:0007829|PDB:1KNX"
FT   HELIX           305..308
FT                   /evidence="ECO:0007829|PDB:1KNX"
SQ   SEQUENCE   312 AA;  35234 MW;  475F6B73587517C1 CRC64;
     MKKLLVKELI EQFQDCVNLI DGHTNTSNVI RVPGLKRVVF EMLGLFSSQI GSVAILGKRE
     FGFLSQKTLV EQQQILHNLL KLNPPAIILT KSFTDPTVLL QVNQTYQVPI LKTDFFSTEL
     SFTVETYINE QFATVAQIHG VLLEVFGVGV LLTGRSGIGK SECALDLINK NHLFVGDDAI
     EIYRLGNRLF GRAQEVAKKF MEIRGLGIIN VERFYGLQIT KQRTEIQLMV NLLSLEKQTT
     VTFERLGTEL KKQRLLGVDL SFYEIPISPG RKTSEIIESA VIDFKLKHSG YNSALDFIEN
     QKAILKRKKD ES
//