PANE_THEKO
ID PANE_THEKO Reviewed; 309 AA.
AC Q5JGC2;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=2-dehydropantoate 2-reductase {ECO:0000305};
DE EC=1.1.1.169 {ECO:0000269|PubMed:23941541};
DE AltName: Full=Ketopantoate reductase {ECO:0000303|PubMed:23941541};
DE Short=KPR {ECO:0000303|PubMed:23941541};
GN OrderedLocusNames=TK1968 {ECO:0000312|EMBL:BAD86157.1};
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, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, PATHWAY, SUBUNIT, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=ATCC BAA-918 / JCM 12380 / KOD1;
RX PubMed=23941541; DOI=10.1111/mmi.12363;
RA Tomita H., Imanaka T., Atomi H.;
RT "Identification and characterization of an archaeal ketopantoate reductase
RT and its involvement in regulation of coenzyme A biosynthesis.";
RL Mol. Microbiol. 90:307-321(2013).
RN [3] {ECO:0007744|PDB:5HWS}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH NADP, SUBUNIT, AND
RP MUTAGENESIS OF TYR-60 AND TRP-129.
RX PubMed=27139828; DOI=10.1107/s2053230x16005033;
RA Aikawa Y., Nishitani Y., Tomita H., Atomi H., Miki K.;
RT "Crystal structure of ketopantoate reductase from Thermococcus kodakarensis
RT complexed with NADP(+).";
RL Acta Crystallogr. F 72:369-375(2016).
RN [4] {ECO:0007744|PDB:5AYV}
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) IN COMPLEX WITH 2-DEHYDROPANTOATE;
RP COENZYME A AND NADP, ACTIVITY REGULATION, SUBUNIT, DOMAIN, AND MUTAGENESIS
RP OF CYS-84.
RX PubMed=26757028; DOI=10.1002/prot.24984;
RA Aikawa Y., Nishitani Y., Tomita H., Atomi H., Miki K.;
RT "Crystal structure of archaeal ketopantoate reductase complexed with
RT coenzyme a and 2-oxopantoate provides structural insights into feedback
RT regulation.";
RL Proteins 84:374-382(2016).
CC -!- FUNCTION: Catalyzes the NAD(P)H-dependent reduction of ketopantoate
CC into pantoic acid. Prefers NADH rather than NADPH as the electron
CC donor. {ECO:0000269|PubMed:23941541}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-pantoate + NAD(+) = 2-dehydropantoate + H(+) + NADH;
CC Xref=Rhea:RHEA:61292, ChEBI:CHEBI:11561, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15980, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:23941541};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:61294;
CC Evidence={ECO:0000269|PubMed:23941541};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-pantoate + NADP(+) = 2-dehydropantoate + H(+) + NADPH;
CC Xref=Rhea:RHEA:16233, ChEBI:CHEBI:11561, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15980, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.169; Evidence={ECO:0000269|PubMed:23941541};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16235;
CC Evidence={ECO:0000269|PubMed:23941541};
CC -!- ACTIVITY REGULATION: Regulated by feedback inhibition by coenzyme A
CC (CoA). CoA acts by competing with NAD(P)H (PubMed:23941541,
CC PubMed:26757028). A disulfide bond is formed between CoA and Cys-84,
CC which indicates an irreversible inhibition upon binding of CoA
CC (PubMed:26757028). {ECO:0000269|PubMed:23941541,
CC ECO:0000269|PubMed:26757028}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.03 uM for ketopantoate {ECO:0000269|PubMed:23941541};
CC KM=3.01 uM for NADH {ECO:0000269|PubMed:23941541};
CC KM=1.35 uM for NADPH {ECO:0000269|PubMed:23941541};
CC KM=130 uM for D-pantoate {ECO:0000269|PubMed:23941541};
CC KM=2040 uM for L-pantoate {ECO:0000269|PubMed:23941541};
CC KM=40.9 uM for NAD(+) {ECO:0000269|PubMed:23941541};
CC Vmax=40.7 umol/min/mg enzyme toward ketopantoate (in the presence of
CC NADH) {ECO:0000269|PubMed:23941541};
CC Vmax=34.7 umol/min/mg enzyme toward NADH
CC {ECO:0000269|PubMed:23941541};
CC Vmax=3.92 umol/min/mg enzyme toward NADPH
CC {ECO:0000269|PubMed:23941541};
CC Note=kcat is 23.1 sec(-1) toward ketopantoate (in the presence of
CC NADH). kcat is 19.7 sec(-1) toward NADH. kcat is 2.22 sec(-1) toward
CC NADPH. {ECO:0000269|PubMed:23941541};
CC pH dependence:
CC Optimum pH is 6.4. {ECO:0000269|PubMed:23941541};
CC Temperature dependence:
CC Optimum temperature is 90 degrees Celsius. Is extremely thermostable.
CC {ECO:0000269|PubMed:23941541};
CC -!- PATHWAY: Cofactor biosynthesis; coenzyme A biosynthesis.
CC {ECO:0000305|PubMed:23941541}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:23941541,
CC ECO:0000269|PubMed:26757028, ECO:0000269|PubMed:27139828}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:23941541}.
CC -!- DOMAIN: Cooperative binding of CoA and ketopantoate induces a closed
CC inhibited state by interacting with the N-terminal and C-terminal
CC domains, and seems to facilitate the disulfide bond formation.
CC {ECO:0000269|PubMed:26757028}.
CC -!- DISRUPTION PHENOTYPE: Disruption of the gene results in a strain with
CC growth defects that are complemented by addition of pantoate.
CC {ECO:0000269|PubMed:23941541}.
CC -!- SIMILARITY: Belongs to the ketopantoate reductase family.
CC {ECO:0000305}.
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DR EMBL; AP006878; BAD86157.1; -; Genomic_DNA.
DR RefSeq; WP_011250918.1; NC_006624.1.
DR PDB; 5AYV; X-ray; 1.65 A; A/B=1-309.
DR PDB; 5HWS; X-ray; 2.30 A; A/B/C/D=1-309.
DR PDBsum; 5AYV; -.
DR PDBsum; 5HWS; -.
DR AlphaFoldDB; Q5JGC2; -.
DR SMR; Q5JGC2; -.
DR STRING; 69014.TK1968; -.
DR EnsemblBacteria; BAD86157; BAD86157; TK1968.
DR GeneID; 3234733; -.
DR KEGG; tko:TK1968; -.
DR PATRIC; fig|69014.16.peg.1922; -.
DR eggNOG; arCOG04139; Archaea.
DR HOGENOM; CLU_031468_0_1_2; -.
DR InParanoid; Q5JGC2; -.
DR OMA; NYSSMYQ; -.
DR OrthoDB; 57213at2157; -.
DR PhylomeDB; Q5JGC2; -.
DR BioCyc; MetaCyc:MON-21895; -.
DR BRENDA; 1.1.1.169; 5246.
DR UniPathway; UPA00241; -.
DR Proteomes; UP000000536; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0008677; F:2-dehydropantoate 2-reductase activity; IDA:CACAO.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0015937; P:coenzyme A biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0015940; P:pantothenate biosynthetic process; IEA:InterPro.
DR Gene3D; 1.10.1040.10; -; 1.
DR InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR InterPro; IPR013328; 6PGD_dom2.
DR InterPro; IPR003710; ApbA.
DR InterPro; IPR013752; KPA_reductase.
DR InterPro; IPR013332; KPR_N.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF02558; ApbA; 1.
DR Pfam; PF08546; ApbA_C; 1.
DR SUPFAM; SSF48179; SSF48179; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR00745; apbA_panE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coenzyme A biosynthesis; Cytoplasm; NAD; NADP;
KW Nucleotide-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..309
FT /note="2-dehydropantoate 2-reductase"
FT /id="PRO_0000448239"
FT ACT_SITE 180
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P0A9J4"
FT BINDING 7..12
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:26757028,
FT ECO:0000269|PubMed:27139828"
FT BINDING 8..10
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|PubMed:26757028"
FT BINDING 31
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|PubMed:26757028"
FT BINDING 31
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:26757028"
FT BINDING 74
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|PubMed:26757028"
FT BINDING 74
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:27139828"
FT BINDING 84
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|PubMed:26757028"
FT BINDING 100
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:26757028,
FT ECO:0000269|PubMed:27139828"
FT BINDING 124
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:26757028,
FT ECO:0000269|PubMed:27139828"
FT BINDING 180
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26757028"
FT BINDING 184
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26757028"
FT BINDING 188
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26757028"
FT BINDING 198
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26757028"
FT BINDING 247..250
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:26757028"
FT BINDING 257
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|PubMed:26757028"
FT BINDING 262
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:26757028,
FT ECO:0000269|PubMed:27139828"
FT MUTAGEN 60
FT /note="Y->A: Decreases efficiency of the inhibition by
FT CoA."
FT /evidence="ECO:0000269|PubMed:27139828"
FT MUTAGEN 84
FT /note="C->A: Decreases efficiency of the inhibition by CoA.
FT Inhibition shows no time-dependency."
FT /evidence="ECO:0000269|PubMed:26757028"
FT MUTAGEN 129
FT /note="W->A: Decreases efficiency of the inhibition by
FT CoA."
FT /evidence="ECO:0000269|PubMed:27139828"
FT STRAND 2..6
FT /evidence="ECO:0007829|PDB:5AYV"
FT HELIX 10..21
FT /evidence="ECO:0007829|PDB:5AYV"
FT STRAND 25..29
FT /evidence="ECO:0007829|PDB:5AYV"
FT HELIX 32..41
FT /evidence="ECO:0007829|PDB:5AYV"
FT STRAND 43..49
FT /evidence="ECO:0007829|PDB:5AYV"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:5AYV"
FT STRAND 56..60
FT /evidence="ECO:0007829|PDB:5AYV"
FT STRAND 67..71
FT /evidence="ECO:0007829|PDB:5AYV"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:5AYV"
FT HELIX 78..85
FT /evidence="ECO:0007829|PDB:5AYV"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:5AYV"
FT STRAND 94..97
FT /evidence="ECO:0007829|PDB:5AYV"
FT STRAND 100..103
FT /evidence="ECO:0007829|PDB:5AYV"
FT HELIX 104..108
FT /evidence="ECO:0007829|PDB:5AYV"
FT TURN 109..111
FT /evidence="ECO:0007829|PDB:5AYV"
FT STRAND 115..120
FT /evidence="ECO:0007829|PDB:5AYV"
FT STRAND 123..128
FT /evidence="ECO:0007829|PDB:5AYV"
FT STRAND 131..136
FT /evidence="ECO:0007829|PDB:5AYV"
FT STRAND 140..148
FT /evidence="ECO:0007829|PDB:5AYV"
FT HELIX 151..162
FT /evidence="ECO:0007829|PDB:5AYV"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:5AYV"
FT HELIX 173..194
FT /evidence="ECO:0007829|PDB:5AYV"
FT HELIX 200..203
FT /evidence="ECO:0007829|PDB:5AYV"
FT HELIX 205..224
FT /evidence="ECO:0007829|PDB:5AYV"
FT HELIX 233..243
FT /evidence="ECO:0007829|PDB:5AYV"
FT TURN 244..246
FT /evidence="ECO:0007829|PDB:5HWS"
FT HELIX 250..257
FT /evidence="ECO:0007829|PDB:5AYV"
FT HELIX 263..265
FT /evidence="ECO:0007829|PDB:5AYV"
FT HELIX 267..276
FT /evidence="ECO:0007829|PDB:5AYV"
FT HELIX 282..299
FT /evidence="ECO:0007829|PDB:5AYV"
SQ SEQUENCE 309 AA; 34050 MW; 265F1F3C5C4A96FD CRC64;
MRIYVLGAGS IGSLFGALLA RAGNDVTLIG RREQVDAINK NGLHVFGAEE FTVKPKATIY
APEEPPDLLI LAVKSYSTKT ALECARQCIG RNTWVLSIQN GLGNEELALK YTPNVMGGVT
TNGAMLVEWG KVLWAGKGIT VIGRYPTGRD DFVDEVASVF NEAGIDTSVT ENAIGWKWAK
AIVNSVINGL GTVLEVKNGH LKDDPHLEGI SVDIAREGCM VAQQLGIEFE IHPLELLWDT
IERTRENYNS TLQDIWRGRE TEVDYIHGKI VEYARSVGME APRNELLWVL VKAKERINRG
KTRNISEGC
