LDHD_LACDA
ID LDHD_LACDA Reviewed; 333 AA.
AC P26297; Q1G7V7;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=D-lactate dehydrogenase;
DE Short=D-LDH;
DE EC=1.1.1.28;
DE AltName: Full=D-specific 2-hydroxyacid dehydrogenase;
GN Name=ldhA; OrderedLocusNames=Ldb0101;
OS Lactobacillus delbrueckii subsp. bulgaricus (strain ATCC 11842 / DSM 20081
OS / BCRC 10696 / JCM 1002 / NBRC 13953 / NCIMB 11778 / NCTC 12712 / WDCM
OS 00102 / Lb 14).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Lactobacillaceae;
OC Lactobacillus.
OX NCBI_TaxID=390333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1915894; DOI=10.1016/0014-5793(91)81226-x;
RA Bernard N., Ferain T., Garmyn D., Hols P., Delcour J.;
RT "Cloning of the D-lactate dehydrogenase gene from Lactobacillus delbrueckii
RT subsp. bulgaricus by complementation in Escherichia coli.";
RL FEBS Lett. 290:61-64(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=1569100; DOI=10.1016/s0021-9258(18)42473-8;
RA Kochhar S., Hunziker P., Leong-Morgenthaler P.M., Hottinger H.;
RT "Primary structure, physicochemical properties, and chemical modification
RT of NAD(+)-dependent D-lactate dehydrogenase. Evidence for the presence of
RT Arg-235, His-303, Tyr-101, and Trp-19 at or near the active site.";
RL J. Biol. Chem. 267:8499-8513(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1610363; DOI=10.1016/0006-291x(92)91683-h;
RA Kochhar S., Chuard N., Hottinger H.;
RT "Cloning and overexpression of the Lactobacillus bulgaricus NAD(+)-
RT dependent D-lactate dehydrogenase gene in Escherichia coli: purification
RT and characterization of the recombinant enzyme.";
RL Biochem. Biophys. Res. Commun. 185:705-712(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 11842 / DSM 20081 / BCRC 10696 / JCM 1002 / NBRC 13953 / NCIMB
RC 11778 / NCTC 12712 / WDCM 00102 / Lb 14;
RX PubMed=16754859; DOI=10.1073/pnas.0603024103;
RA van de Guchte M., Penaud S., Grimaldi C., Barbe V., Bryson K., Nicolas P.,
RA Robert C., Oztas S., Mangenot S., Couloux A., Loux V., Dervyn R., Bossy R.,
RA Bolotin A., Batto J.-M., Walunas T., Gibrat J.-F., Bessieres P.,
RA Weissenbach J., Ehrlich S.D., Maguin E.;
RT "The complete genome sequence of Lactobacillus bulgaricus reveals extensive
RT and ongoing reductive evolution.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:9274-9279(2006).
RN [5]
RP SIMILARITY TO OTHER ENZYMES OF THIS FAMILY.
RX PubMed=1567457; DOI=10.1080/02500169208537781;
RA Kochhar S., Hunziker P., Leong-Morgenthaler P.M., Hottinger H.;
RT "Evolutionary relationship of NAD(+)-dependent D-lactate dehydrogenase:
RT comparison of primary structure of 2-hydroxy acid dehydrogenases.";
RL Biochem. Biophys. Res. Commun. 184:60-66(1992).
RN [6]
RP ACTIVE SITE, AND MUTAGENESIS OF HIS-206; ARG-236; ASP-260; GLU-265 AND
RP HIS-297.
RX PubMed=9063466; DOI=10.1111/j.1432-1033.1997.00213.x;
RA Bernard N., Johnsen K., Gelpi J.L., Alvarez J.A., Ferain T., Garmyn D.,
RA Hols P., Cortes A., Clarke A.R., Holbrook J.J., Delcour J.;
RT "D-2-hydroxy-4-methylvalerate dehydrogenase from Lactobacillus delbrueckii
RT subsp. bulgaricus. II. Mutagenic analysis of catalytically important
RT residues.";
RL Eur. J. Biochem. 244:213-219(1997).
RN [7]
RP 3D-STRUCTURE MODELING.
RX PubMed=8476420; DOI=10.1006/bbrc.1993.1398;
RA Vinals C., Depiereux E., Feytmans E.;
RT "Prediction of structurally conserved regions of D-specific hydroxy acid
RT dehydrogenases by multiple alignment with formate dehydrogenase.";
RL Biochem. Biophys. Res. Commun. 192:182-188(1993).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH NAD, AND SUBUNIT.
RX PubMed=12054772; DOI=10.1016/s0022-2836(02)00086-4;
RA Razeto A., Kochhar S., Hottinger H., Dauter M., Wilson K.S., Lamzin V.S.;
RT "Domain closure, substrate specificity and catalysis of D-lactate
RT dehydrogenase from Lactobacillus bulgaricus.";
RL J. Mol. Biol. 318:109-119(2002).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-lactate + NAD(+) = H(+) + NADH + pyruvate;
CC Xref=Rhea:RHEA:16369, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16004, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.28;
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12054772}.
CC -!- SIMILARITY: Belongs to the D-isomer specific 2-hydroxyacid
CC dehydrogenase family. {ECO:0000305}.
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DR EMBL; X60220; CAA42781.1; -; Genomic_DNA.
DR EMBL; M85224; AAA25246.1; -; Genomic_DNA.
DR EMBL; CR954253; CAI96942.1; -; Genomic_DNA.
DR PIR; A38094; A38094.
DR RefSeq; WP_011543503.1; NZ_JQAV01000045.1.
DR PDB; 1J49; X-ray; 2.20 A; A/B=1-333.
DR PDB; 1J4A; X-ray; 1.90 A; A/B/C/D=1-333.
DR PDBsum; 1J49; -.
DR PDBsum; 1J4A; -.
DR AlphaFoldDB; P26297; -.
DR SMR; P26297; -.
DR STRING; 390333.Ldb0101; -.
DR EnsemblBacteria; CAI96942; CAI96942; Ldb0101.
DR KEGG; ldb:Ldb0101; -.
DR PATRIC; fig|390333.13.peg.1571; -.
DR eggNOG; COG1052; Bacteria.
DR HOGENOM; CLU_019796_1_1_9; -.
DR OMA; VIVTAHQ; -.
DR BioCyc; LDEL390333:LDB_RS00400-MON; -.
DR BRENDA; 1.1.1.28; 2853.
DR SABIO-RK; P26297; -.
DR EvolutionaryTrace; P26297; -.
DR Proteomes; UP000001259; Chromosome.
DR GO; GO:0008720; F:D-lactate dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR InterPro; IPR006139; D-isomer_2_OHA_DH_cat_dom.
DR InterPro; IPR029753; D-isomer_DH_CS.
DR InterPro; IPR029752; D-isomer_DH_CS1.
DR InterPro; IPR006140; D-isomer_DH_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF00389; 2-Hacid_dh; 1.
DR Pfam; PF02826; 2-Hacid_dh_C; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00065; D_2_HYDROXYACID_DH_1; 1.
DR PROSITE; PS00670; D_2_HYDROXYACID_DH_2; 1.
DR PROSITE; PS00671; D_2_HYDROXYACID_DH_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; NAD; Oxidoreductase;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..333
FT /note="D-lactate dehydrogenase"
FT /id="PRO_0000075953"
FT ACT_SITE 236
FT /evidence="ECO:0000305|PubMed:9063466"
FT ACT_SITE 265
FT /evidence="ECO:0000305|PubMed:9063466"
FT ACT_SITE 297
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:9063466"
FT BINDING 156..157
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12054772,
FT ECO:0007744|PDB:1J49"
FT BINDING 176
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12054772,
FT ECO:0007744|PDB:1J49"
FT BINDING 207..208
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12054772"
FT BINDING 213
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12054772,
FT ECO:0007744|PDB:1J49"
FT BINDING 234..236
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000305|PubMed:12054772"
FT BINDING 260
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12054772,
FT ECO:0007744|PDB:1J49"
FT MUTAGEN 206
FT /note="H->Q: Increase of activity."
FT /evidence="ECO:0000269|PubMed:9063466"
FT MUTAGEN 236
FT /note="R->K: Decrease of activity."
FT /evidence="ECO:0000269|PubMed:9063466"
FT MUTAGEN 260
FT /note="D->N: Decrease of activity."
FT /evidence="ECO:0000269|PubMed:9063466"
FT MUTAGEN 265
FT /note="E->Q: Decrease of activity."
FT /evidence="ECO:0000269|PubMed:9063466"
FT MUTAGEN 297
FT /note="H->Q: 90% loss of activity."
FT /evidence="ECO:0000269|PubMed:9063466"
FT CONFLICT 41
FT /note="V -> A (in Ref. 2; AAA25246)"
FT /evidence="ECO:0000305"
FT CONFLICT 117
FT /note="R -> A (in Ref. 1; CAA42781)"
FT /evidence="ECO:0000305"
FT CONFLICT 122
FT /note="D -> A (in Ref. 2; AAA25246)"
FT /evidence="ECO:0000305"
FT CONFLICT 152
FT /note="I -> V (in Ref. 2; AAA25246)"
FT /evidence="ECO:0000305"
FT CONFLICT 174
FT /note="A -> T (in Ref. 1; CAA42781)"
FT /evidence="ECO:0000305"
FT CONFLICT 220
FT /note="E -> K (in Ref. 2; AAA25246)"
FT /evidence="ECO:0000305"
FT CONFLICT 254
FT /note="I -> V (in Ref. 2; AAA25246)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="I -> V (in Ref. 2; AAA25246)"
FT /evidence="ECO:0000305"
FT CONFLICT 273
FT /note="W -> R (in Ref. 2; AAA25246)"
FT /evidence="ECO:0000305"
FT STRAND 3..6
FT /evidence="ECO:0007829|PDB:1J4A"
FT HELIX 11..13
FT /evidence="ECO:0007829|PDB:1J4A"
FT HELIX 14..22
FT /evidence="ECO:0007829|PDB:1J4A"
FT STRAND 27..31
FT /evidence="ECO:0007829|PDB:1J4A"
FT TURN 38..40
FT /evidence="ECO:0007829|PDB:1J4A"
FT HELIX 41..44
FT /evidence="ECO:0007829|PDB:1J4A"
FT STRAND 48..52
FT /evidence="ECO:0007829|PDB:1J4A"
FT HELIX 60..68
FT /evidence="ECO:0007829|PDB:1J4A"
FT STRAND 73..79
FT /evidence="ECO:0007829|PDB:1J4A"
FT HELIX 86..91
FT /evidence="ECO:0007829|PDB:1J4A"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:1J4A"
FT HELIX 104..120
FT /evidence="ECO:0007829|PDB:1J4A"
FT HELIX 122..130
FT /evidence="ECO:0007829|PDB:1J4A"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:1J4A"
FT STRAND 147..152
FT /evidence="ECO:0007829|PDB:1J4A"
FT HELIX 156..167
FT /evidence="ECO:0007829|PDB:1J4A"
FT STRAND 171..175
FT /evidence="ECO:0007829|PDB:1J4A"
FT HELIX 181..185
FT /evidence="ECO:0007829|PDB:1J4A"
FT HELIX 193..199
FT /evidence="ECO:0007829|PDB:1J4A"
FT STRAND 201..205
FT /evidence="ECO:0007829|PDB:1J4A"
FT HELIX 211..213
FT /evidence="ECO:0007829|PDB:1J4A"
FT HELIX 219..224
FT /evidence="ECO:0007829|PDB:1J4A"
FT STRAND 229..233
FT /evidence="ECO:0007829|PDB:1J4A"
FT HELIX 237..239
FT /evidence="ECO:0007829|PDB:1J4A"
FT HELIX 242..250
FT /evidence="ECO:0007829|PDB:1J4A"
FT STRAND 253..260
FT /evidence="ECO:0007829|PDB:1J4A"
FT TURN 266..270
FT /evidence="ECO:0007829|PDB:1J4A"
FT HELIX 281..288
FT /evidence="ECO:0007829|PDB:1J4A"
FT STRAND 292..294
FT /evidence="ECO:0007829|PDB:1J4A"
FT HELIX 303..321
FT /evidence="ECO:0007829|PDB:1J4A"
FT STRAND 327..329
FT /evidence="ECO:0007829|PDB:1J4A"
SQ SEQUENCE 333 AA; 37049 MW; 16E8B68D54B9D9D4 CRC64;
MTKIFAYAIR EDEKPFLKEW EDAHKDVEVE YTDKLLTPET VALAKGADGV VVYQQLDYTA
ETLQALADNG ITKMSLRNVG VDNIDMAKAK ELGFQITNVP VYSPNAIAEH AAIQAARILR
QDKAMDEKVA RHDLRWAPTI GREVRDQVVG VIGTGHIGQV FMQIMEGFGA KVIAYDIFRN
PELEKKGYYV DSLDDLYKQA DVISLHVPDV PANVHMINDE SIAKMKQDVV IVNVSRGPLV
DTDAVIRGLD SGKIFGYAMD VYEGEVGIFN EDWEGKEFPD ARLADLIARP NVLVTPHTAF
YTTHAVRNMV VKAFDNNLEL VEGKEAETPV KVG
