LDH_THEMA
ID LDH_THEMA Reviewed; 319 AA.
AC P16115;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=L-lactate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000303|PubMed:2318202};
DE Short=L-LDH {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000303|PubMed:2318202};
DE EC=1.1.1.27 {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000269|PubMed:2318202};
GN Name=ldh {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000303|PubMed:8404889};
GN OrderedLocusNames=TM_1867;
OS Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826
OS / MSB8).
OC Bacteria; Thermotogae; Thermotogales; Thermotogaceae; Thermotoga.
OX NCBI_TaxID=243274;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8;
RX PubMed=8404889; DOI=10.1111/j.1432-1033.1993.tb18190.x;
RA Ostendorp R., Liebl W., Schurig H., Jaenicke R.;
RT "The L-lactate dehydrogenase gene of the hyperthermophilic bacterium
RT Thermotoga maritima cloned by complementation in Escherichia coli.";
RL Eur. J. Biochem. 216:709-715(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8;
RX PubMed=10360571; DOI=10.1038/20601;
RA Nelson K.E., Clayton R.A., Gill S.R., Gwinn M.L., Dodson R.J., Haft D.H.,
RA Hickey E.K., Peterson J.D., Nelson W.C., Ketchum K.A., McDonald L.A.,
RA Utterback T.R., Malek J.A., Linher K.D., Garrett M.M., Stewart A.M.,
RA Cotton M.D., Pratt M.S., Phillips C.A., Richardson D.L., Heidelberg J.F.,
RA Sutton G.G., Fleischmann R.D., Eisen J.A., White O., Salzberg S.L.,
RA Smith H.O., Venter J.C., Fraser C.M.;
RT "Evidence for lateral gene transfer between Archaea and Bacteria from
RT genome sequence of Thermotoga maritima.";
RL Nature 399:323-329(1999).
RN [3]
RP PROTEIN SEQUENCE OF 1-31, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, ACTIVITY REGULATION, SUBUNIT, AND SUBSTRATE SPECIFICITY.
RC STRAIN=ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8;
RX PubMed=2318202; DOI=10.1111/j.1432-1033.1990.tb15388.x;
RA Wrba A., Jaenicke R., Huber R., Stetter K.O.;
RT "Lactate dehydrogenase from the extreme thermophile Thermotoga maritima.";
RL Eur. J. Biochem. 188:195-201(1990).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH NAD AND FRUCTOSE
RP 1,6-BISPHOSPHATE, ACTIVE SITE, AND SUBUNIT.
RX PubMed=9655830; DOI=10.1016/s0969-2126(98)00078-1;
RA Auerbach G., Ostendorp R., Prade L., Korndorfer I., Dams T., Huber R.,
RA Jaenicke R.;
RT "Lactate dehydrogenase from the hyperthermophilic bacterium Thermotoga
RT maritima: the crystal structure at 2.1-A resolution reveals strategies for
RT intrinsic protein stabilization.";
RL Structure 6:769-781(1998).
CC -!- FUNCTION: Catalyzes the conversion of lactate to pyruvate. It is
CC stereospecific for L(+)-lactate. {ECO:0000255|HAMAP-Rule:MF_00488,
CC ECO:0000269|PubMed:2318202}.
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:0000269|PubMed:2318202};
CC -!- ACTIVITY REGULATION: Allosterically activated by fructose 1,6-
CC bisphosphate (FBP). Inactivated by Mn(2+), Co(2+), Cd(2+) and Zn(2+).
CC {ECO:0000269|PubMed:2318202}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=30 uM for NADH (at 55 degrees Celsius and in the absence of
CC fructose 1,6-bisphosphate (FBP)) {ECO:0000269|PubMed:2318202};
CC KM=60 uM for pyruvate (at 55 degrees Celsius and in the presence of
CC fructose 1,6-bisphosphate (FBP)) {ECO:0000269|PubMed:2318202};
CC KM=90 uM for NAD(+) (at 55 degrees Celsius and in the absence of
CC fructose 1,6-bisphosphate (FBP)) {ECO:0000269|PubMed:2318202};
CC KM=3.7 mM for pyruvate (at 55 degrees Celsius and in the absence of
CC fructose 1,6-bisphosphate (FBP)) {ECO:0000269|PubMed:2318202};
CC KM=25 mM for L(+)-lactate (at 55 degrees Celsius and in the presence
CC of fructose 1,6-bisphosphate (FBP)) {ECO:0000269|PubMed:2318202};
CC KM=410 mM for L(+)-lactate (at 55 degrees Celsius and in the absence
CC of fructose 1,6-bisphosphate (FBP)) {ECO:0000269|PubMed:2318202};
CC pH dependence:
CC Optimum pH is 7. {ECO:0000269|PubMed:2318202};
CC Temperature dependence:
CC Long-term stability up to 80 degrees Celsius. Fructose 1,6-
CC bisphosphate (FBP) increases the thermal stability at 90 degrees
CC Celsius (pH 6.0). {ECO:0000269|PubMed:2318202};
CC -!- PATHWAY: Fermentation; pyruvate fermentation to lactate; (S)-lactate
CC from pyruvate: step 1/1. {ECO:0000255|HAMAP-Rule:MF_00488}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_00488,
CC ECO:0000269|PubMed:2318202, ECO:0000269|PubMed:9655830}.
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; X74302; CAA52355.1; -; Genomic_DNA.
DR EMBL; AE000512; AAD36929.1; -; Genomic_DNA.
DR PIR; S36863; S36863.
DR RefSeq; NP_229663.1; NC_000853.1.
DR RefSeq; WP_004082418.1; NZ_CP011107.1.
DR PDB; 1A5Z; X-ray; 2.10 A; A=1-319.
DR PDBsum; 1A5Z; -.
DR AlphaFoldDB; P16115; -.
DR SMR; P16115; -.
DR STRING; 243274.THEMA_04835; -.
DR DrugBank; DB03940; Oxamic Acid.
DR EnsemblBacteria; AAD36929; AAD36929; TM_1867.
DR KEGG; tma:TM1867; -.
DR eggNOG; COG0039; Bacteria.
DR InParanoid; P16115; -.
DR OMA; CYIIVLT; -.
DR OrthoDB; 870724at2; -.
DR UniPathway; UPA00554; UER00611.
DR EvolutionaryTrace; P16115; -.
DR Proteomes; UP000008183; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004459; F:L-lactate dehydrogenase activity; IBA:GO_Central.
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; Reference proteome.
FT CHAIN 1..319
FT /note="L-lactate dehydrogenase"
FT /id="PRO_0000168406"
FT ACT_SITE 172
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000305|PubMed:9655830"
FT BINDING 10..11
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:9655830,
FT ECO:0007744|PDB:1A5Z"
FT BINDING 32
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000269|PubMed:9655830, ECO:0007744|PDB:1A5Z"
FT BINDING 37
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 62
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 76..77
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 79
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 85
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 115..117
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 117..120
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 140
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 145..148
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 150
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 BINDING 165
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:9655830, ECO:0007744|PDB:1A5Z"
FT BINDING 226
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT MOD_RES 217
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT CONFLICT 14
FT /note="Missing (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 2..6
FT /evidence="ECO:0007829|PDB:1A5Z"
FT HELIX 10..22
FT /evidence="ECO:0007829|PDB:1A5Z"
FT STRAND 26..31
FT /evidence="ECO:0007829|PDB:1A5Z"
FT HELIX 35..48
FT /evidence="ECO:0007829|PDB:1A5Z"
FT HELIX 49..51
FT /evidence="ECO:0007829|PDB:1A5Z"
FT STRAND 56..59
FT /evidence="ECO:0007829|PDB:1A5Z"
FT HELIX 62..65
FT /evidence="ECO:0007829|PDB:1A5Z"
FT STRAND 69..73
FT /evidence="ECO:0007829|PDB:1A5Z"
FT HELIX 85..106
FT /evidence="ECO:0007829|PDB:1A5Z"
FT STRAND 111..114
FT /evidence="ECO:0007829|PDB:1A5Z"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:1A5Z"
FT HELIX 119..130
FT /evidence="ECO:0007829|PDB:1A5Z"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:1A5Z"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:1A5Z"
FT HELIX 143..157
FT /evidence="ECO:0007829|PDB:1A5Z"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:1A5Z"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:1A5Z"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:1A5Z"
FT HELIX 190..194
FT /evidence="ECO:0007829|PDB:1A5Z"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:1A5Z"
FT HELIX 202..223
FT /evidence="ECO:0007829|PDB:1A5Z"
FT HELIX 228..242
FT /evidence="ECO:0007829|PDB:1A5Z"
FT STRAND 247..258
FT /evidence="ECO:0007829|PDB:1A5Z"
FT STRAND 263..273
FT /evidence="ECO:0007829|PDB:1A5Z"
FT STRAND 276..280
FT /evidence="ECO:0007829|PDB:1A5Z"
FT HELIX 287..308
FT /evidence="ECO:0007829|PDB:1A5Z"
SQ SEQUENCE 319 AA; 34994 MW; A1FB9B97CDCF290B CRC64;
MKIGIVGLGR VGSSTAFALL MKGFAREMVL IDVDKKRAEG DALDLIHGTP FTRRANIYAG
DYADLKGSDV VIVAAGVPQK PGETRLQLLG RNARVMKEIA RNVSKYAPDS IVIVVTNPVD
VLTYFFLKES GMDPRKVFGS GTVLDTARLR TLIAQHCGFS PRSVHVYVIG EHGDSEVPVW
SGAMIGGIPL QNMCQICQKC DSKILENFAE KTKRAAYEII ERKGATHYAI ALAVADIVES
IFFDEKRVLT LSVYLEDYLG VKDLCISVPV TLGKHGVERI LELNLNEEEL EAFRKSASIL
KNAINEITAE ENKHQNTSG
