PPS_THEKO
ID PPS_THEKO Reviewed; 261 AA.
AC Q5JIZ8;
DT 31-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=4-phosphopantoate--beta-alanine ligase {ECO:0000255|HAMAP-Rule:MF_02224, ECO:0000305};
DE EC=6.3.2.36 {ECO:0000255|HAMAP-Rule:MF_02224, ECO:0000269|PubMed:19666462, ECO:0000269|PubMed:22940806, ECO:0000269|PubMed:24638914};
DE AltName: Full=Phosphopantothenate synthetase {ECO:0000255|HAMAP-Rule:MF_02224, ECO:0000303|PubMed:19666462};
DE Short=PPS {ECO:0000255|HAMAP-Rule:MF_02224, ECO:0000303|PubMed:19666462};
GN OrderedLocusNames=TK1686;
OS Thermococcus kodakarensis (strain ATCC BAA-918 / JCM 12380 / KOD1)
OS (Pyrococcus kodakaraensis (strain KOD1)).
OC Archaea; Euryarchaeota; Thermococci; Thermococcales; Thermococcaceae;
OC Thermococcus.
OX NCBI_TaxID=69014;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-918 / JCM 12380 / KOD1;
RX PubMed=15710748; DOI=10.1101/gr.3003105;
RA Fukui T., Atomi H., Kanai T., Matsumi R., Fujiwara S., Imanaka T.;
RT "Complete genome sequence of the hyperthermophilic archaeon Thermococcus
RT kodakaraensis KOD1 and comparison with Pyrococcus genomes.";
RL Genome Res. 15:352-363(2005).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, ROLE IN COA BIOSYNTHESIS, PATHWAY, SUBUNIT,
RP AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC BAA-918 / JCM 12380 / KOD1;
RX PubMed=19666462; DOI=10.1074/jbc.m109.009696;
RA Yokooji Y., Tomita H., Atomi H., Imanaka T.;
RT "Pantoate kinase and phosphopantothenate synthetase, two novel enzymes
RT necessary for CoA biosynthesis in the Archaea.";
RL J. Biol. Chem. 284:28137-28145(2009).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RC STRAIN=ATCC BAA-918 / JCM 12380 / KOD1;
RX PubMed=22940806; DOI=10.1007/s00792-012-0477-5;
RA Ishibashi T., Tomita H., Yokooji Y., Morikita T., Watanabe B., Hiratake J.,
RA Kishimoto A., Kita A., Miki K., Imanaka T., Atomi H.;
RT "A detailed biochemical characterization of phosphopantothenate synthetase,
RT a novel enzyme involved in coenzyme A biosynthesis in the Archaea.";
RL Extremophiles 16:819-828(2012).
RN [4] {ECO:0007744|PDB:3WDK, ECO:0007744|PDB:3WDL, ECO:0007744|PDB:3WDM}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEXES WITH ATP; REACTION
RP INTERMEDIATE AND ADENOSINE, FUNCTION, CATALYTIC ACTIVITY, REACTION
RP MECHANISM, SUBUNIT, AND MUTAGENESIS OF ARG-17 AND TYR-45.
RX PubMed=24638914; DOI=10.1002/prot.24546;
RA Kishimoto A., Kita A., Ishibashi T., Tomita H., Yokooji Y., Imanaka T.,
RA Atomi H., Miki K.;
RT "Crystal structure of phosphopantothenate synthetase from Thermococcus
RT kodakarensis.";
RL Proteins 82:1924-1936(2014).
CC -!- FUNCTION: Catalyzes the condensation of (R)-4-phosphopantoate and beta-
CC alanine to 4'-phosphopantothenate in the CoA biosynthesis pathway
CC (PubMed:19666462, PubMed:22940806, PubMed:24638914). Cannot use (R)-
CC pantoate as substrate and thus does not display pantothenate synthetase
CC (PS) activity (PubMed:19666462, PubMed:22940806). Displays strict
CC specificity for its natural substrates, 4-phosphopantoate, ATP and
CC beta-alanine (PubMed:22940806). {ECO:0000269|PubMed:19666462,
CC ECO:0000269|PubMed:22940806, ECO:0000269|PubMed:24638914}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-4-phosphopantoate + ATP + beta-alanine = (R)-4'-
CC phosphopantothenate + AMP + diphosphate + H(+); Xref=Rhea:RHEA:27930,
CC ChEBI:CHEBI:10986, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57966, ChEBI:CHEBI:61294,
CC ChEBI:CHEBI:456215; EC=6.3.2.36; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_02224, ECO:0000269|PubMed:19666462,
CC ECO:0000269|PubMed:22940806, ECO:0000269|PubMed:24638914};
CC -!- ACTIVITY REGULATION: Activity is not affected by 4'-phosphopantothenate
CC or CoA/acetyl-CoA. {ECO:0000269|PubMed:22940806}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.34 mM for beta-alanine {ECO:0000269|PubMed:22940806};
CC KM=1.16 mM for 4-phosphopantoate {ECO:0000269|PubMed:22940806};
CC KM=2.44 mM for ATP {ECO:0000269|PubMed:22940806};
CC Vmax=6.38 umol/min/mg enzyme toward beta-alanine
CC {ECO:0000269|PubMed:22940806};
CC Vmax=15.6 umol/min/mg enzyme toward 4-phosphopantoate
CC {ECO:0000269|PubMed:22940806};
CC Vmax=14.7 umol/min/mg enzyme toward ATP
CC {ECO:0000269|PubMed:22940806};
CC pH dependence:
CC Optimum pH is 6.5. {ECO:0000269|PubMed:22940806};
CC Temperature dependence:
CC Activity increases with temperature elevation from 65 degrees Celsius
CC to 95 degrees Celsius. {ECO:0000269|PubMed:22940806};
CC -!- PATHWAY: Cofactor biosynthesis; coenzyme A biosynthesis.
CC {ECO:0000255|HAMAP-Rule:MF_02224, ECO:0000269|PubMed:19666462}.
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_02224,
CC ECO:0000269|PubMed:19666462, ECO:0000269|PubMed:24638914}.
CC -!- DISRUPTION PHENOTYPE: Only viable in the presence of CoA or 4'-
CC phosphopantothenate. {ECO:0000269|PubMed:19666462}.
CC -!- SIMILARITY: Belongs to the archaeal phosphopantothenate synthetase
CC family. {ECO:0000255|HAMAP-Rule:MF_02224, ECO:0000305}.
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DR EMBL; AP006878; BAD85875.1; -; Genomic_DNA.
DR RefSeq; WP_011250637.1; NC_006624.1.
DR PDB; 3WDK; X-ray; 2.30 A; A/B/C/D=1-261.
DR PDB; 3WDL; X-ray; 2.40 A; A/B/C/D=1-261.
DR PDB; 3WDM; X-ray; 2.00 A; A/B/C/D=1-261.
DR PDBsum; 3WDK; -.
DR PDBsum; 3WDL; -.
DR PDBsum; 3WDM; -.
DR AlphaFoldDB; Q5JIZ8; -.
DR SMR; Q5JIZ8; -.
DR STRING; 69014.TK1686; -.
DR EnsemblBacteria; BAD85875; BAD85875; TK1686.
DR GeneID; 3235144; -.
DR KEGG; tko:TK1686; -.
DR PATRIC; fig|69014.16.peg.1643; -.
DR eggNOG; arCOG04262; Archaea.
DR HOGENOM; CLU_078701_0_0_2; -.
DR InParanoid; Q5JIZ8; -.
DR OMA; PKSHPRY; -.
DR OrthoDB; 76877at2157; -.
DR PhylomeDB; Q5JIZ8; -.
DR BioCyc; MetaCyc:MON-15971; -.
DR BRENDA; 6.3.2.26; 5246.
DR BRENDA; 6.3.2.36; 5246.
DR UniPathway; UPA00241; -.
DR Proteomes; UP000000536; Chromosome.
DR GO; GO:0016881; F:acid-amino acid ligase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0015937; P:coenzyme A biosynthetic process; IEA:UniProtKB-UniRule.
DR Gene3D; 3.40.50.12640; -; 1.
DR HAMAP; MF_02224; PPS; 1.
DR InterPro; IPR002855; PPS/PS.
DR InterPro; IPR038138; PPS/PS_sf.
DR PANTHER; PTHR40695; PTHR40695; 1.
DR Pfam; PF02006; PPS_PS; 1.
DR PIRSF; PIRSF004853; UCP004853; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Coenzyme A biosynthesis; Ligase;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..261
FT /note="4-phosphopantoate--beta-alanine ligase"
FT /id="PRO_0000409260"
FT BINDING 17
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:B6YXQ1, ECO:0000255|HAMAP-
FT Rule:MF_02224"
FT BINDING 39
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02224,
FT ECO:0000269|PubMed:24638914, ECO:0007744|PDB:3WDL"
FT BINDING 181..183
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02224,
FT ECO:0000269|PubMed:24638914, ECO:0007744|PDB:3WDL"
FT BINDING 187..188
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02224,
FT ECO:0000269|PubMed:24638914, ECO:0007744|PDB:3WDL"
FT BINDING 199..200
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02224,
FT ECO:0000269|PubMed:24638914, ECO:0007744|PDB:3WDL"
FT MUTAGEN 17
FT /note="R->A: Strong decrease in activity."
FT /evidence="ECO:0000269|PubMed:24638914"
FT MUTAGEN 45
FT /note="Y->A,F: Strong decrease in activity."
FT /evidence="ECO:0000269|PubMed:24638914"
FT HELIX 11..25
FT /evidence="ECO:0007829|PDB:3WDM"
FT HELIX 31..47
FT /evidence="ECO:0007829|PDB:3WDM"
FT HELIX 53..68
FT /evidence="ECO:0007829|PDB:3WDM"
FT STRAND 73..76
FT /evidence="ECO:0007829|PDB:3WDM"
FT HELIX 78..83
FT /evidence="ECO:0007829|PDB:3WDM"
FT HELIX 85..95
FT /evidence="ECO:0007829|PDB:3WDM"
FT STRAND 98..101
FT /evidence="ECO:0007829|PDB:3WDM"
FT HELIX 108..119
FT /evidence="ECO:0007829|PDB:3WDM"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:3WDL"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:3WDM"
FT TURN 148..150
FT /evidence="ECO:0007829|PDB:3WDM"
FT HELIX 151..153
FT /evidence="ECO:0007829|PDB:3WDM"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:3WDM"
FT HELIX 164..172
FT /evidence="ECO:0007829|PDB:3WDM"
FT STRAND 176..180
FT /evidence="ECO:0007829|PDB:3WDM"
FT HELIX 187..191
FT /evidence="ECO:0007829|PDB:3WDM"
FT STRAND 192..196
FT /evidence="ECO:0007829|PDB:3WDM"
FT HELIX 200..213
FT /evidence="ECO:0007829|PDB:3WDM"
FT TURN 214..216
FT /evidence="ECO:0007829|PDB:3WDK"
FT HELIX 219..227
FT /evidence="ECO:0007829|PDB:3WDM"
FT HELIX 231..252
FT /evidence="ECO:0007829|PDB:3WDM"
SQ SEQUENCE 261 AA; 29845 MW; D36C99384454D82E CRC64;
MVNIPKSHPR YWSLYYREKI IEGMEKGMTA KAGLIAHGRG EAFDYLIGER TIEPAERAMR
AAVAKFLLAE HPVISVNGNV AALVPKETIE LAKALNAKLE INLFYRTEER VRTIAEELRK
YDPEIEILGI NPTKRIPGLE HERGKVDENG IWKADVVLVP LEDGDRTEAL VRMGKFVVTV
DLNPLSRSAR MADITIVDNI VRAYPRMVEL AREMKDYSRE ELLKIVGEYD NGKTLSDVLL
HIRDRLTRLA EEGIWRRKEL E
