LDH_LACCA
ID LDH_LACCA Reviewed; 326 AA.
AC P00343;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=L-lactate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000303|PubMed:1768113};
DE Short=L-LDH {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000303|PubMed:1768113};
DE EC=1.1.1.27 {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000269|PubMed:14601, ECO:0000269|PubMed:7766183, ECO:0000305|PubMed:19787773};
GN Name=ldh {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000303|PubMed:1768113};
OS Lactobacillus casei.
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Lactobacillaceae;
OC Lacticaseibacillus.
OX NCBI_TaxID=1582;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=ATCC 393 / DSM 20011 / BCRC 10697 / JCM 1134 / NBRC 15883 / NCIMB
RC 11970 / NCDO 161 / WDCM 00100;
RX PubMed=1768113; DOI=10.1128/aem.57.8.2413-2417.1991;
RA Kim S.F., Baek S.J., Pack M.Y.;
RT "Cloning and nucleotide sequence of the Lactobacillus casei lactate
RT dehydrogenase gene.";
RL Appl. Environ. Microbiol. 57:2413-2417(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 393 / DSM 20011 / BCRC 10697 / JCM 1134 / NBRC 15883 / NCIMB
RC 11970 / NCDO 161 / WDCM 00100;
RA Taguchi H., Ohta T.;
RL Submitted (NOV-1991) to the PIR data bank.
RN [3]
RP PARTIAL PROTEIN SEQUENCE.
RC STRAIN=ATCC 393 / DSM 20011 / BCRC 10697 / JCM 1134 / NBRC 15883 / NCIMB
RC 11970 / NCDO 161 / WDCM 00100;
RX PubMed=6411465; DOI=10.1111/j.1432-1033.1983.tb07595.x;
RA Hensel R., Mayr U., Yang C.;
RT "The complete primary structure of the allosteric L-lactate dehydrogenase
RT from Lactobacillus casei.";
RL Eur. J. Biochem. 134:503-511(1983).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RX PubMed=14601; DOI=10.1007/bf00446658;
RA Hensel R., Mayr U., Stetter K.O., Kandler O.;
RT "Comparative studies of lactic acid dehydrogenases in lactic acid bacteria.
RT I. Purification and kinetics of the allosteric L-lactic acid dehydrogenase
RT from Lactobacillus casei ssp. casei and Lactobacillus curvatus.";
RL Arch. Microbiol. 112:81-93(1977).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-174, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND ACTIVITY REGULATION.
RC STRAIN=ATCC 393 / DSM 20011 / BCRC 10697 / JCM 1134 / NBRC 15883 / NCIMB
RC 11970 / NCDO 161 / WDCM 00100;
RX PubMed=7766183; DOI=10.1271/bbb.59.451;
RA Taguchi H., Ohta T.;
RT "Role of histidine 188 in fructose 1,6-bisphosphate- and divalent cation-
RT regulated L-lactate dehydrogenase of Lactobacillus casei.";
RL Biosci. Biotechnol. Biochem. 59:451-458(1995).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 2-326 IN COMPLEX WITH FRUCTOSE
RP 1,6-BISPHOSPHATE ANALOG, AND ACTIVE SITE.
RA Buehner M., Hecht H.J.;
RT "Structure determination of the allosteric L-lactate dehydrogenase from
RT Lactobacillus-casei at 3A resolution.";
RL Acta Crystallogr. A 40:32-34(1984).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS,
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, MUTAGENESIS OF ARG-171,
RP AND SUBUNIT.
RX PubMed=19787773; DOI=10.1002/prot.22597;
RA Arai K., Ishimitsu T., Fushinobu S., Uchikoba H., Matsuzawa H., Taguchi H.;
RT "Active and inactive state structures of unliganded Lactobacillus casei
RT allosteric L-lactate dehydrogenase.";
RL Proteins 78:681-694(2010).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) IN COMPLEX WITH FRUCTOSE
RP 1,6-BISPHOSPHATE AND SUBSTRATE ANALOGS, ACTIVE SITE, AND SUBUNIT.
RA Arai K., Miyanaga A., Uchikoba H., Fushinobu S., Taguchi H.;
RT "Crystal structure of penta mutant of L-lactate dehydrogenase from
RT Lactobacillus casei.";
RL Submitted (MAR-2012) to the PDB data bank.
CC -!- FUNCTION: Catalyzes the conversion of lactate to pyruvate.
CC {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000269|PubMed:14601,
CC ECO:0000269|PubMed:19787773, ECO:0000269|PubMed:7766183,
CC ECO:0000305|PubMed:1768113}.
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, ECO:0000269|PubMed:14601,
CC ECO:0000269|PubMed:7766183, ECO:0000305|PubMed:19787773};
CC -!- ACTIVITY REGULATION: Allosterically activated by fructose 1,6-
CC bisphosphate (FBP) alone under acidic conditions, while it requires
CC additional activation factors such as divalent cations (Mn(2+)) under
CC neutral conditions (PubMed:14601, PubMed:7766183). Under acidic
CC conditions, Mn(2+) is an inhibitor in the absence of fructose 1,6-
CC bisphosphate (FBP) (PubMed:14601, PubMed:7766183). In case of L.casei,
CC L-LDH binds four fructose 1,6-bisphosphate (FBP) molecules per
CC tetramer, while usual allosteric L-LDH binds only two fructose 1,6-
CC bisphosphate (FBP) molecules per tetramer (PubMed:14601,
CC PubMed:7766183). {ECO:0000269|PubMed:14601, ECO:0000269|PubMed:7766183,
CC ECO:0000305|PubMed:19787773}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.45 mM for pyruvate (at pH 4.8) {ECO:0000269|PubMed:14601};
CC KM=0.71 mM for pyruvate (at pH 5.5) {ECO:0000269|PubMed:14601};
CC KM=3 mM for pyruvate (at pH 6.2) {ECO:0000269|PubMed:14601};
CC KM=12 mM for pyruvate (at pH 7) {ECO:0000269|PubMed:14601};
CC Vmax=2500 umol/min/mg enzyme with pyruvate as substrate (at pH 6.2)
CC {ECO:0000269|PubMed:14601};
CC Vmax=2400 umol/min/mg enzyme with pyruvate as substrate (at pH 7)
CC {ECO:0000269|PubMed:14601};
CC Vmax=2000 umol/min/mg enzyme with pyruvate as substrate (at pH 5.5)
CC {ECO:0000269|PubMed:14601};
CC Vmax=1900 umol/min/mg enzyme with pyruvate as substrate (at pH 4.8)
CC {ECO:0000269|PubMed:14601};
CC Temperature dependence:
CC Thermostable up to 50 degrees Celsius. Thermostabilized in the
CC presence of both fructose 1,6-bisphosphate (FBP) and Mn(2+) ions.
CC {ECO:0000269|PubMed:14601, ECO:0000269|PubMed:7766183};
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:19787773, ECO:0000305|Ref.8}.
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; D12591; BAA02133.1; -; Genomic_DNA.
DR EMBL; M76708; AAA25245.2; -; Genomic_DNA.
DR PIR; A43944; DELBLA.
DR RefSeq; WP_003567646.1; NZ_MODT01000075.1.
DR PDB; 1LLC; X-ray; 3.00 A; A=2-326.
DR PDB; 2ZQY; X-ray; 2.60 A; A/B/C/D=1-326.
DR PDB; 2ZQZ; X-ray; 2.50 A; A/B/C/D/E/F=1-326.
DR PDB; 6J9S; X-ray; 2.00 A; A/B/C/D/E/F=1-326.
DR PDB; 6J9T; X-ray; 2.70 A; A/B/C/D/E/F=1-326.
DR PDB; 6J9U; X-ray; 2.79 A; A/B/C/D/E/F=1-326.
DR PDB; 6JML; X-ray; 2.30 A; A/B/C/D/E/F=1-326.
DR PDBsum; 1LLC; -.
DR PDBsum; 2ZQY; -.
DR PDBsum; 2ZQZ; -.
DR PDBsum; 6J9S; -.
DR PDBsum; 6J9T; -.
DR PDBsum; 6J9U; -.
DR PDBsum; 6JML; -.
DR AlphaFoldDB; P00343; -.
DR SMR; P00343; -.
DR STRING; 1582.AAW28_10185; -.
DR GeneID; 45549606; -.
DR eggNOG; COG0039; Bacteria.
DR OMA; ASCAEYI; -.
DR BioCyc; MetaCyc:MON-8681; -.
DR SABIO-RK; P00343; -.
DR UniPathway; UPA00554; UER00611.
DR EvolutionaryTrace; P00343; -.
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; Direct protein sequencing; NAD;
KW Oxidoreductase; Phosphoprotein.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:6411465"
FT CHAIN 2..326
FT /note="L-lactate dehydrogenase"
FT /id="PRO_0000168347"
FT ACT_SITE 181
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000305|Ref.6, ECO:0000305|Ref.8, ECO:0007744|PDB:1LLC,
FT ECO:0007744|PDB:6J9T, ECO:0007744|PDB:6J9U"
FT BINDING 20
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 41
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 46
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 71
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 85..86
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 88
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 94
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000269|Ref.8, ECO:0007744|PDB:6J9U"
FT BINDING 107
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 124..126
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 126..129
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000305|Ref.8, ECO:0007744|PDB:6J9U"
FT BINDING 149
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT BINDING 154..157
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000305|Ref.8, ECO:0007744|PDB:6J9S,
FT ECO:0007744|PDB:6J9T, ECO:0007744|PDB:6J9U"
FT BINDING 159
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|Ref.8, ECO:0007744|PDB:6J9T,
FT ECO:0007744|PDB:6J9U"
FT BINDING 171..174
FT /ligand="beta-D-fructose 1,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:32966"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PDB:6J9T"
FT BINDING 174
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 235
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488,
FT ECO:0000269|Ref.8, ECO:0007744|PDB:6J9S,
FT ECO:0007744|PDB:6J9U"
FT MOD_RES 226
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00488"
FT MUTAGEN 171
FT /note="R->Q: Exhibits no significant catalytic activity
FT toward pyruvate up to 50 mM at pH 5.0 in the absence of
FT fructose 1,6-bisphosphate (FBP). In the presence of 5 mM
FT fructose 1,6-bisphosphate (FBP), it exhibits marked
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:19787773"
FT MUTAGEN 174
FT /note="H->D: Shows a lower thermoresistance than the wild-
FT type, even in the absence of fructose 1,6-bisphosphate
FT (FBP). Not thermostabilized in the presence of fructose
FT 1,6-bisphosphate (FBP), Mn(2+) or both. Under acidic
FT conditions, the mutant does not show a positive allosteric
FT regulation by fructose 1,6-bisphosphate (FBP), which even
FT inhibits the stimulative effects of the alternative
FT activation factors. In addition, Mn(2+) ions also show
FT greatly reduced inhibitory effects on the mutant enzyme.
FT Under neutral conditions, the reaction of the mutant is
FT slightly enhanced by fructose 1,6-bisphosphate (FBP), but
FT not further stimulates by additional Mn(2+) ions, unlike
FT the case of the wild-type."
FT /evidence="ECO:0000269|PubMed:7766183"
FT CONFLICT 26
FT /note="Y -> F (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 52
FT /note="I -> T (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 88..89
FT /note="QK -> KQ (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="G -> L (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 270
FT /note="L -> I (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 273
FT /note="I -> L (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 5..7
FT /evidence="ECO:0007829|PDB:6JML"
FT STRAND 11..15
FT /evidence="ECO:0007829|PDB:6JML"
FT HELIX 19..31
FT /evidence="ECO:0007829|PDB:6JML"
FT STRAND 35..40
FT /evidence="ECO:0007829|PDB:6JML"
FT HELIX 44..55
FT /evidence="ECO:0007829|PDB:6JML"
FT HELIX 56..60
FT /evidence="ECO:0007829|PDB:6JML"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:6JML"
FT HELIX 71..76
FT /evidence="ECO:0007829|PDB:6JML"
FT STRAND 78..82
FT /evidence="ECO:0007829|PDB:6JML"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:1LLC"
FT HELIX 94..114
FT /evidence="ECO:0007829|PDB:6JML"
FT STRAND 119..123
FT /evidence="ECO:0007829|PDB:6JML"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:6JML"
FT HELIX 128..139
FT /evidence="ECO:0007829|PDB:6JML"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:6JML"
FT STRAND 146..148
FT /evidence="ECO:0007829|PDB:6JML"
FT HELIX 152..166
FT /evidence="ECO:0007829|PDB:6JML"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:6JML"
FT STRAND 177..182
FT /evidence="ECO:0007829|PDB:6JML"
FT HELIX 189..191
FT /evidence="ECO:0007829|PDB:6JML"
FT HELIX 199..205
FT /evidence="ECO:0007829|PDB:6JML"
FT HELIX 211..222
FT /evidence="ECO:0007829|PDB:6JML"
FT HELIX 224..232
FT /evidence="ECO:0007829|PDB:6JML"
FT HELIX 237..251
FT /evidence="ECO:0007829|PDB:6JML"
FT STRAND 256..266
FT /evidence="ECO:0007829|PDB:6JML"
FT HELIX 267..269
FT /evidence="ECO:0007829|PDB:6JML"
FT STRAND 271..282
FT /evidence="ECO:0007829|PDB:6JML"
FT STRAND 285..289
FT /evidence="ECO:0007829|PDB:6JML"
FT HELIX 296..316
FT /evidence="ECO:0007829|PDB:6JML"
FT HELIX 318..323
FT /evidence="ECO:0007829|PDB:2ZQY"
SQ SEQUENCE 326 AA; 35531 MW; 934905641592AF8A CRC64;
MASITDKDHQ KVILVGDGAV GSSYAYAMVL QGIAQEIGIV DIFKDKTKGD AIDLSNALPF
TSPKKIYSAE YSDAKDADLV VITAGAPQKP GETRLDLVNK NLKILKSIVD PIVDSGFNGI
FLVAANPVDI LTYATWKLSG FPKNRVVGSG TSLDTARFRQ SIAEMVNVDA RSVHAYIMGE
HGDTEFPVWS HANIGGVTIA EWVKAHPEIK EDKLVKMFED VRDAAYEIIK LKGATFYGIA
TALARISKAI LNDENAVLPL SVYMDGQYGL NDIYIGTPAV INRNGIQNIL EIPLTDHEEE
SMQKSASQLK KVLTDAFAKN DIETRQ
