HPRK_MYCPN
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 03-AUG-2022, entry version 137.
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) (Mycoplasmoides
OS pneumoniae).
OC Bacteria; Tenericutes; Mollicutes; Mycoplasmataceae; Mycoplasma.
OX NCBI_TaxID=272634;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 29342 / M129;
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 (PubMed:12368461 and PubMed:12589763) called
CC HPr kinase/phosphatase, but P-Ser-HPr dephosphorylation was shown in
CC several bacteria 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}.
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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; NC_000912.1.
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 PRIDE; P75548; -.
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 OMA; AMNNRQK; -.
DR BioCyc; MPNE272634:G1GJ3-358-MON; -.
DR EvolutionaryTrace; P75548; -.
DR Proteomes; UP000000808; Chromosome.
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 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
