LDH_GEOSE
ID LDH_GEOSE Reviewed; 317 AA.
AC P00344;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=L-lactate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000303|PubMed:3026926};
DE Short=L-LDH {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000303|PubMed:3026926};
DE EC=1.1.1.27 {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000305|PubMed:3580377};
GN Name=ldh {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000303|PubMed:3026926};
GN Synonyms=lct;
OS Geobacillus stearothermophilus (Bacillus stearothermophilus).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Geobacillus.
OX NCBI_TaxID=1422;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3026926; DOI=10.1016/0378-1119(86)90165-4;
RA Barstow D.A., Clarke A.R., Chia W.N., Wigley D., Sharman A.F.,
RA Holbrook J.J., Atkinson T., Minton N.P.;
RT "Cloning, expression and complete nucleotide sequence of the Bacillus
RT stearothermophilus L-lactate dehydrogenase gene.";
RL Gene 46:47-55(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3675869; DOI=10.1515/bchm3.1987.368.2.1167;
RA Zuelli F., Weber H., Zuber H.;
RT "Structure and function of L-lactate dehydrogenases from thermophilic and
RT mesophilic bacteria, VI. Nucleotide sequences of lactate dehydrogenase
RT genes from the thermophilic bacteria Bacillus stearothermophilus, B.
RT caldolyticus and B. caldotenax.";
RL Biol. Chem. Hoppe-Seyler 368:1167-1177(1987).
RN [3]
RP PARTIAL PROTEIN SEQUENCE.
RC STRAIN=ATCC 29609 / DSM 2027 / NCA 1503 / NCIMB 8924;
RX PubMed=6618448; DOI=10.1515/bchm2.1983.364.2.879;
RA Tratschin J.D., Wirz B., Frank G., Zuber H.;
RT "Structure and function of L-lactate dehydrogenases from thermophilic and
RT mesophilic bacteria. II) The primary structure of thermophilic lactate
RT dehydrogenase from Bacillus stearothermophilus. Cyanogen bromide fragments
RT and partial sequence.";
RL Hoppe-Seyler's Z. Physiol. Chem. 364:879-892(1983).
RN [4]
RP PARTIAL PROTEIN SEQUENCE.
RC STRAIN=ATCC 29609 / DSM 2027 / NCA 1503 / NCIMB 8924;
RX PubMed=6352452; DOI=10.1515/bchm2.1983.364.2.893;
RA Wirz B., Suter F., Zuber H.;
RT "Structure and function of L-lactate dehydrogenases from thermophilic and
RT mesophilic bacteria. III) The primary structure of thermophilic lactate
RT dehydrogenase from Bacillus stearothermophilus. Hydroxylamine-, o-
RT iodosobenzoic acid- and tryptic-fragments. The complete amino-acid
RT sequence.";
RL Hoppe-Seyler's Z. Physiol. Chem. 364:893-909(1983).
RN [5]
RP FUNCTION, ACTIVITY REGULATION, AND SUBUNIT.
RA Clarke A.R., Atkinson T., Campbell J.W., Holbrook J.J.;
RT "The assembly mechanism of the lactate dehydrogenase tetramer from Bacillus
RT stearothermophilus; the equilibrium relationships between quaternary
RT structure and the binding of fructose 1,6-biphosphate, NADH and oxamate.";
RL Biochim. Biophys. Acta 829:387-396(1985).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, MUTAGENESIS OF ARG-157,
RP AND SUBUNIT.
RX PubMed=3580377; DOI=10.1016/0167-4838(87)90234-2;
RA Clarke A.R., Wigley D.B., Barstow D.A., Chia W.N., Atkinson T.,
RA Holbrook J.J.;
RT "A single amino acid substitution deregulates a bacterial lactate
RT dehydrogenase and stabilizes its tetrameric structure.";
RL Biochim. Biophys. Acta 913:72-80(1987).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) IN COMPLEX WITH NAD AND FRUCTOSE
RP 1,6-BISPHOSPHATE, AND SUBUNIT.
RX PubMed=2330370; DOI=10.1002/prot.340070108;
RA Piontek K., Chakrabarti P., Schar H.P., Rossmann M.G., Zuber H.;
RT "Structure determination and refinement of Bacillus stearothermophilus
RT lactate dehydrogenase.";
RL Proteins 7:74-92(1990).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH NAD; FRUCTOSE
RP 1,6-BISPHOSPHATE AND SUBSTRATE ANALOG, ACTIVITY REGULATION, ACTIVE SITE,
RP AND SUBUNIT.
RX PubMed=1731077; DOI=10.1016/0022-2836(92)90733-z;
RA Wigley D.B., Gamblin S.J., Turkenburg J.P., Dodson E.J., Piontek K.,
RA Muirhead H., Holbrook J.J.;
RT "Structure of a ternary complex of an allosteric lactate dehydrogenase from
RT Bacillus stearothermophilus at 2.5-A resolution.";
RL J. Mol. Biol. 223:317-335(1992).
CC -!- FUNCTION: Catalyzes the conversion of lactate to pyruvate.
CC {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000269|PubMed:3580377,
CC ECO:0000269|Ref.5}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-lactate + NAD(+) = H(+) + NADH + pyruvate;
CC Xref=Rhea:RHEA:23444, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16651, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.27;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00488,
CC ECO:0000305|PubMed:3580377};
CC -!- ACTIVITY REGULATION: Allosterically activated by fructose 1,6-
CC bisphosphate (FBP). The improvement in affinity for substrate occurs in
CC two steps; the binding of fructose 1,6-bisphosphate (FBP) to the dimer,
CC and the dimer to tetramer conversion. {ECO:0000269|PubMed:3580377,
CC ECO:0000269|Ref.5, ECO:0000305|PubMed:1731077}.
CC -!- PATHWAY: Fermentation; pyruvate fermentation to lactate; (S)-lactate
CC from pyruvate: step 1/1. {ECO:0000255|HAMAP-Rule:MF_00488}.
CC -!- SUBUNIT: Exists as a dimer and a tetramer (dimer of dimers). The
CC conversion occurs via the binding of fructose 1,6-bisphosphate (FBP) to
CC the dimer. {ECO:0000269|PubMed:1731077, ECO:0000269|PubMed:2330370,
CC ECO:0000269|PubMed:3580377, ECO:0000305|Ref.5}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00488}.
CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. LDH family.
CC {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000305}.
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DR EMBL; M14788; AAA22568.1; -; Genomic_DNA.
DR EMBL; M19396; AAA22567.1; -; Genomic_DNA.
DR PIR; A26053; DEBSLF.
DR RefSeq; WP_033016716.1; NZ_RCTK01000052.1.
DR PDB; 1LDB; X-ray; 2.80 A; A/B/C/D=1-317.
DR PDB; 1LDN; X-ray; 2.50 A; A/B/C/D/E/F/G/H=1-316.
DR PDB; 2LDB; X-ray; 3.00 A; A/B/C/D=1-317.
DR PDBsum; 1LDB; -.
DR PDBsum; 1LDN; -.
DR PDBsum; 2LDB; -.
DR AlphaFoldDB; P00344; -.
DR SMR; P00344; -.
DR GeneID; 58574470; -.
DR BRENDA; 1.1.1.27; 623.
DR SABIO-RK; P00344; -.
DR UniPathway; UPA00554; UER00611.
DR EvolutionaryTrace; P00344; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004459; F:L-lactate dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0051287; F:NAD binding; IDA:UniProtKB.
DR GO; GO:0006096; P:glycolytic process; IEA:UniProtKB-UniRule.
DR Gene3D; 3.90.110.10; -; 1.
DR HAMAP; MF_00488; Lactate_dehydrog; 1.
DR InterPro; IPR001557; L-lactate/malate_DH.
DR InterPro; IPR011304; L-lactate_DH.
DR InterPro; IPR018177; L-lactate_DH_AS.
DR InterPro; IPR022383; Lactate/malate_DH_C.
DR InterPro; IPR001236; Lactate/malate_DH_N.
DR InterPro; IPR015955; Lactate_DH/Glyco_Ohase_4_C.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF02866; Ldh_1_C; 1.
DR Pfam; PF00056; Ldh_1_N; 1.
DR PIRSF; PIRSF000102; Lac_mal_DH; 1.
DR PRINTS; PR00086; LLDHDRGNASE.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF56327; SSF56327; 1.
DR TIGRFAMs; TIGR01771; L-LDH-NAD; 1.
DR PROSITE; PS00064; L_LDH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; Cytoplasm; Direct protein sequencing; NAD;
KW Oxidoreductase; Phosphoprotein.
FT CHAIN 1..317
FT /note="L-lactate dehydrogenase"
FT /id="PRO_0000168328"
FT ACT_SITE 179
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000305|PubMed:1731077, ECO:0007744|PDB:1LDN"
FT BINDING 16..17
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000269|PubMed:1731077, ECO:0000269|PubMed:2330370,
FT ECO:0007744|PDB:1LDN, ECO:0007744|PDB:2LDB"
FT BINDING 38
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000269|PubMed:1731077, ECO:0000269|PubMed:2330370,
FT ECO:0007744|PDB:1LDN, ECO:0007744|PDB:2LDB"
FT BINDING 43
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 69
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 83..84
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 86
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 92
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000305|PubMed:1731077, ECO:0007744|PDB:1LDN"
FT BINDING 105
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 122..124
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000269|PubMed:1731077, ECO:0000269|PubMed:2330370,
FT ECO:0007744|PDB:1LDN, ECO:0007744|PDB:2LDB"
FT BINDING 124..127
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 147
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:1731077,
FT ECO:0000269|PubMed:2330370, ECO:0007744|PDB:1LDN,
FT ECO:0007744|PDB:2LDB"
FT BINDING 152..155
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000305|PubMed:1731077, ECO:0007744|PDB:1LDN"
FT BINDING 157
FT /ligand="beta-D-fructose 1,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:32966"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000269|PubMed:2330370, ECO:0007744|PDB:2LDB"
FT BINDING 169..172
FT /ligand="beta-D-fructose 1,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:32966"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:1731077,
FT ECO:0000269|PubMed:2330370, ECO:0007744|PDB:1LDN,
FT ECO:0007744|PDB:2LDB"
FT BINDING 233
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000305|PubMed:1731077, ECO:0007744|PDB:1LDN"
FT MOD_RES 224
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT MUTAGEN 157
FT /note="R->Q: This mutant undergoes a reversible subunit
FT assembly from dimer to tetramer. However, the tetramer
FT mutant is much more stable than the wild type, and is
FT destabilized rather than stabilized by binding the
FT allosteric regulator, fructose 1,6-bisphosphate (FBP). The
FT mutation weakens the binding of fructose 1,6-bisphosphate
FT (FBP) to both the dimeric and tetrameric forms, and almost
FT abolishes any stimulatory effect."
FT /evidence="ECO:0000269|PubMed:3580377"
FT CONFLICT 113
FT /note="S -> H (in Ref. 2; AAA22567)"
FT /evidence="ECO:0000305"
FT TURN 2..5
FT /evidence="ECO:0007829|PDB:1LDN"
FT STRAND 8..12
FT /evidence="ECO:0007829|PDB:1LDN"
FT HELIX 16..28
FT /evidence="ECO:0007829|PDB:1LDN"
FT STRAND 32..37
FT /evidence="ECO:0007829|PDB:1LDN"
FT HELIX 41..54
FT /evidence="ECO:0007829|PDB:1LDN"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:1LDN"
FT STRAND 63..66
FT /evidence="ECO:0007829|PDB:1LDN"
FT HELIX 69..71
FT /evidence="ECO:0007829|PDB:1LDN"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:1LDN"
FT STRAND 76..80
FT /evidence="ECO:0007829|PDB:1LDN"
FT TURN 88..90
FT /evidence="ECO:0007829|PDB:1LDN"
FT HELIX 93..95
FT /evidence="ECO:0007829|PDB:1LDN"
FT HELIX 96..113
FT /evidence="ECO:0007829|PDB:1LDN"
FT STRAND 117..121
FT /evidence="ECO:0007829|PDB:1LDN"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:1LDN"
FT HELIX 126..137
FT /evidence="ECO:0007829|PDB:1LDN"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:1LDN"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:1LDN"
FT HELIX 150..164
FT /evidence="ECO:0007829|PDB:1LDN"
FT HELIX 168..170
FT /evidence="ECO:0007829|PDB:1LDN"
FT STRAND 171..177
FT /evidence="ECO:0007829|PDB:1LDN"
FT TURN 179..182
FT /evidence="ECO:0007829|PDB:1LDB"
FT STRAND 184..192
FT /evidence="ECO:0007829|PDB:1LDN"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:1LDN"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:1LDN"
FT TURN 205..207
FT /evidence="ECO:0007829|PDB:1LDN"
FT HELIX 208..230
FT /evidence="ECO:0007829|PDB:1LDN"
FT HELIX 235..249
FT /evidence="ECO:0007829|PDB:1LDN"
FT STRAND 254..264
FT /evidence="ECO:0007829|PDB:1LDN"
FT HELIX 265..267
FT /evidence="ECO:0007829|PDB:2LDB"
FT STRAND 269..280
FT /evidence="ECO:0007829|PDB:1LDN"
FT STRAND 283..287
FT /evidence="ECO:0007829|PDB:1LDN"
FT HELIX 294..313
FT /evidence="ECO:0007829|PDB:1LDN"
SQ SEQUENCE 317 AA; 34863 MW; 4B146CF681C91046 CRC64;
MKNNGGARVV VIGAGFVGAS YVFALMNQGI ADEIVLIDAN ESKAIGDAMD FNHGKVFAPK
PVDIWHGDYD DCRDADLVVI CAGANQKPGE TRLDLVDKNI AIFRSIVESV MASGFQGLFL
VATNPVDILT YATWKFSGLP HERVIGSGTI LDTARFRFLL GEYFSVAPQN VHAYIIGEHG
DTELPVWSQA YIGVMPIRKL VESKGEEAQK DLERIFVNVR DAAYQIIEKK GATYYGIAMG
LARVTRAILH NENAILTVSA YLDGLYGERD VYIGVPAVIN RNGIREVIEI ELNDDEKNRF
HHSAATLKSV LARAFTR
