LDH_THET8
ID LDH_THET8 Reviewed; 310 AA.
AC Q5SJA1;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=L-lactate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000303|PubMed:17936781};
DE Short=L-LDH {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000303|PubMed:17936781};
DE EC=1.1.1.27 {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000269|PubMed:17936781};
GN Name=ldh {ECO:0000255|HAMAP-Rule:MF_00488}; OrderedLocusNames=TTHA1113;
OS Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8).
OC Bacteria; Deinococcus-Thermus; Deinococci; Thermales; Thermaceae; Thermus.
OX NCBI_TaxID=300852;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27634 / DSM 579 / HB8;
RA Masui R., Kurokawa K., Nakagawa N., Tokunaga F., Koyama Y., Shibata T.,
RA Oshima T., Yokoyama S., Yasunaga T., Kuramitsu S.;
RT "Complete genome sequence of Thermus thermophilus HB8.";
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH NAD, AND SUBUNIT.
RA Lokanath N.K., Kunishima N.;
RT "Structure of TT0471 protein from Thermus thermophilus.";
RL Submitted (NOV-2006) to the PDB data bank.
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH NAD AND SUBSTRATE
RP ANALOGS, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP ACTIVE SITE, AND SUBUNIT.
RX PubMed=17936781; DOI=10.1016/j.jmb.2007.09.049;
RA Coquelle N., Fioravanti E., Weik M., Vellieux F., Madern D.;
RT "Activity, stability and structural studies of lactate dehydrogenases
RT adapted to extreme thermal environments.";
RL J. Mol. Biol. 374:547-562(2007).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) IN COMPLEX WITH NAD AND SUBSTRATE
RP ANALOG, ACTIVE SITE, AND SUBUNIT.
RA Diop F., Coquelle N., Tickle J., De Mendoza Barbera E., Vellieux F.M.D.;
RT "Lactate dehydrogenase from T. thermophilus, penta-mutant (ternary complex
RT with AMP).";
RL Submitted (NOV-2010) to the PDB data bank.
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) IN COMPLEX WITH NAD ANALOG, AND
RP SUBUNIT.
RX PubMed=22319152; DOI=10.1093/molbev/mss015;
RA Colletier J.P., Aleksandrov A., Coquelle N., Mraihi S., Mendoza-Barbera E.,
RA Field M., Madern D.;
RT "Sampling the conformational energy landscape of a hyperthermophilic
RT protein by engineering key substitutions.";
RL Mol. Biol. Evol. 29:1683-1694(2012).
CC -!- FUNCTION: Catalyzes the conversion of lactate to pyruvate.
CC {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000269|PubMed:17936781}.
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:17936781};
CC -!- ACTIVITY REGULATION: Allosterically activated by fructose 1,6-
CC bisphosphate (FBP). {ECO:0000255|HAMAP-Rule:MF_00488}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.16 mM for pyruvate {ECO:0000269|PubMed:17936781};
CC Note=kcat is 676 sec(-1) for pyruvate as substrate.
CC {ECO:0000269|PubMed:17936781};
CC Temperature dependence:
CC Optimum temperature is close to 90 degrees Celsius.
CC {ECO:0000269|PubMed:17936781};
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:17936781, ECO:0000269|PubMed:22319152,
CC ECO:0000305|Ref.2, ECO:0000305|Ref.4}.
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}.
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DR EMBL; AP008226; BAD70936.1; -; Genomic_DNA.
DR RefSeq; WP_011228449.1; NC_006461.1.
DR RefSeq; YP_144379.1; NC_006461.1.
DR PDB; 2E37; X-ray; 2.30 A; A/B/C/D/E/F/G/H=1-310.
DR PDB; 2V6M; X-ray; 2.20 A; A/B/C/D=1-310.
DR PDB; 2V7P; X-ray; 2.10 A; A/B/C/D=1-310.
DR PDB; 2XXB; X-ray; 2.15 A; A/B=1-310.
DR PDB; 2XXJ; X-ray; 1.96 A; A/B/C/D=1-310.
DR PDB; 3ZZN; X-ray; 2.90 A; A/B/C/D=1-310.
DR PDB; 4A73; X-ray; 3.00 A; A/B/C/D=1-310.
DR PDBsum; 2E37; -.
DR PDBsum; 2V6M; -.
DR PDBsum; 2V7P; -.
DR PDBsum; 2XXB; -.
DR PDBsum; 2XXJ; -.
DR PDBsum; 3ZZN; -.
DR PDBsum; 4A73; -.
DR AlphaFoldDB; Q5SJA1; -.
DR SMR; Q5SJA1; -.
DR STRING; 300852.55772495; -.
DR EnsemblBacteria; BAD70936; BAD70936; BAD70936.
DR GeneID; 3169622; -.
DR KEGG; ttj:TTHA1113; -.
DR PATRIC; fig|300852.9.peg.1092; -.
DR eggNOG; COG0039; Bacteria.
DR HOGENOM; CLU_045401_1_1_0; -.
DR OMA; CYIIVLT; -.
DR PhylomeDB; Q5SJA1; -.
DR BRENDA; 1.1.1.27; 2305.
DR UniPathway; UPA00554; UER00611.
DR EvolutionaryTrace; Q5SJA1; -.
DR Proteomes; UP000000532; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004459; F:L-lactate dehydrogenase activity; IEA:UniProtKB-UniRule.
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; NAD; Oxidoreductase;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..310
FT /note="L-lactate dehydrogenase"
FT /id="PRO_0000237569"
FT ACT_SITE 172
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000305|PubMed:17936781, ECO:0000305|Ref.4,
FT ECO:0007744|PDB:2V7P, ECO:0007744|PDB:2XXJ"
FT BINDING 10..11
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000269|PubMed:17936781, ECO:0000269|Ref.2,
FT ECO:0000269|Ref.4, ECO:0000305|PubMed:22319152,
FT ECO:0007744|PDB:2E37, ECO:0007744|PDB:2V7P,
FT ECO:0007744|PDB:2XXB, ECO:0007744|PDB:2XXJ,
FT ECO:0007744|PDB:3ZZN"
FT BINDING 32
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000269|PubMed:17936781, ECO:0000269|Ref.2,
FT ECO:0000269|Ref.4, ECO:0000305|PubMed:22319152,
FT ECO:0007744|PDB:2E37, ECO:0007744|PDB:2V7P,
FT ECO:0007744|PDB:2XXB, ECO:0007744|PDB:2XXJ,
FT ECO:0007744|PDB:3ZZN"
FT BINDING 62
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000269|PubMed:17936781, ECO:0000269|Ref.4,
FT ECO:0007744|PDB:2V7P, ECO:0007744|PDB:2XXB,
FT ECO:0007744|PDB:2XXJ"
FT BINDING 76..77
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000269|PubMed:17936781, ECO:0000269|Ref.2,
FT ECO:0000269|Ref.4, ECO:0000305|PubMed:22319152,
FT ECO:0007744|PDB:2E37, ECO:0007744|PDB:2V7P,
FT ECO:0007744|PDB:2XXB, ECO:0007744|PDB:2XXJ,
FT ECO:0007744|PDB:3ZZN"
FT BINDING 79
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000305|PubMed:17936781, ECO:0000305|Ref.4,
FT ECO:0007744|PDB:2V7P, ECO:0007744|PDB:2XXJ"
FT BINDING 85
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:17936781, ECO:0000305|Ref.4,
FT ECO:0007744|PDB:2V7P, ECO:0007744|PDB:2XXJ"
FT BINDING 115..117
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000269|PubMed:17936781, ECO:0000269|Ref.4,
FT ECO:0007744|PDB:2V7P, ECO:0007744|PDB:2XXJ"
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:0000269|PubMed:17936781, ECO:0000269|Ref.4,
FT ECO:0007744|PDB:2V7P, ECO:0007744|PDB:2XXJ"
FT BINDING 145..148
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000305|PubMed:17936781, ECO:0000305|Ref.4,
FT ECO:0007744|PDB:2V7P, ECO:0007744|PDB:2XXJ"
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 BINDING 227
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:17936781, ECO:0000305|Ref.4,
FT ECO:0007744|PDB:2V7P, ECO:0007744|PDB:2XXJ"
FT MOD_RES 218
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT STRAND 2..6
FT /evidence="ECO:0007829|PDB:2XXJ"
FT HELIX 10..21
FT /evidence="ECO:0007829|PDB:2XXJ"
FT STRAND 26..31
FT /evidence="ECO:0007829|PDB:2XXJ"
FT HELIX 35..46
FT /evidence="ECO:0007829|PDB:2XXJ"
FT HELIX 47..51
FT /evidence="ECO:0007829|PDB:2XXJ"
FT STRAND 56..59
FT /evidence="ECO:0007829|PDB:2XXJ"
FT HELIX 62..65
FT /evidence="ECO:0007829|PDB:2XXJ"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:2XXJ"
FT HELIX 85..106
FT /evidence="ECO:0007829|PDB:2XXJ"
FT STRAND 111..114
FT /evidence="ECO:0007829|PDB:2XXJ"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:2XXJ"
FT HELIX 119..130
FT /evidence="ECO:0007829|PDB:2XXJ"
FT HELIX 134..136
FT /evidence="ECO:0007829|PDB:2XXJ"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:2XXJ"
FT HELIX 143..157
FT /evidence="ECO:0007829|PDB:2XXJ"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:2XXJ"
FT STRAND 164..170
FT /evidence="ECO:0007829|PDB:2XXJ"
FT STRAND 177..185
FT /evidence="ECO:0007829|PDB:2XXJ"
FT HELIX 190..196
FT /evidence="ECO:0007829|PDB:2XXJ"
FT HELIX 203..214
FT /evidence="ECO:0007829|PDB:2XXJ"
FT HELIX 216..224
FT /evidence="ECO:0007829|PDB:2XXJ"
FT HELIX 229..243
FT /evidence="ECO:0007829|PDB:2XXJ"
FT STRAND 248..259
FT /evidence="ECO:0007829|PDB:2XXJ"
FT STRAND 262..274
FT /evidence="ECO:0007829|PDB:2XXJ"
FT STRAND 277..281
FT /evidence="ECO:0007829|PDB:2XXJ"
FT HELIX 288..308
FT /evidence="ECO:0007829|PDB:2XXJ"
SQ SEQUENCE 310 AA; 32795 MW; 71D12243E8C00DE4 CRC64;
MKVGIVGSGM VGSATAYALA LLGVAREVVL VDLDRKLAQA HAEDILHATP FAHPVWVRAG
SYGDLEGARA VVLAAGVAQR PGETRLQLLD RNAQVFAQVV PRVLEAAPEA VLLVATNPVD
VMTQVAYRLS GLPPGRVVGS GTILDTARFR ALLAEYLRVA PQSVHAYVLG EHGDSEVLVW
SSAQVGGVPL LEFAEARGRA LSPEDRARID EGVRRAAYRI IEGKGATYYG IGAGLARLVR
AILTDEKGVY TVSAFTPEVE GVLEVSLSLP RILGAGGVEG TVYPSLSPEE REALRRSAEI
LKEAAFALGF
