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Database: UniProt
Entry: P26297
LinkDB: P26297
Original site: P26297 
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   05-DEC-2018, entry version 134.
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
OS   20081 / JCM 1002 / NBRC 13953 / NCIMB 11778).
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
RT   delbrueckii subsp. bulgaricus by complementation in Escherichia
RT   coli.";
RL   FEBS Lett. 290:61-64(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PARTIAL PROTEIN SEQUENCE.
RX   PubMed=1569100;
RA   Kochhar S., Hunziker P., Leong-Morgenthaler P.M., Hottinger H.;
RT   "Primary structure, physicochemical properties, and chemical
RT   modification of NAD(+)-dependent D-lactate dehydrogenase. Evidence for
RT   the presence of Arg-235, His-303, Tyr-101, and Trp-19 at or near the
RT   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:
RT   purification 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 / JCM 1002 / NBRC 13953 / NCIMB 11778;
RX   PubMed=16754859; DOI=10.1073/pnas.0603024103;
RA   van de Guchte M., Penaud S., Grimaldi C., Barbe V., Bryson K.,
RA   Nicolas P., Robert C., Oztas S., Mangenot S., Couloux A., Loux V.,
RA   Dervyn R., Bossy R., Bolotin A., Batto J.-M., Walunas T.,
RA   Gibrat J.-F., Bessieres P., Weissenbach J., Ehrlich S.D., Maguin E.;
RT   "The complete genome sequence of Lactobacillus bulgaricus reveals
RT   extensive 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
RT   dehydrogenase: comparison of primary structure of 2-hydroxy acid
RT   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.,
RA   Garmyn D., Hols P., Cortes A., Clarke A.R., Holbrook J.J., Delcour J.;
RT   "D-2-hydroxy-4-methylvalerate dehydrogenase from Lactobacillus
RT   delbrueckii subsp. bulgaricus. II. Mutagenic analysis of catalytically
RT   important 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
RT   acid dehydrogenases by multiple alignment with formate
RT   dehydrogenase.";
RL   Biochem. Biophys. Res. Commun. 192:182-188(1993).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH NAD, AND
RP   SUBUNIT.
RX   PubMed=12054772; DOI=10.1016/S0022-2836(02)00086-4;
RA   Razeto A., Kochhar S., Hottinger H., Dauter M., Wilson K.S.,
RA   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;
CC         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}.
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; 1DLD; Model; -; A=1-333.
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; 1DLD; -.
DR   PDBsum; 1J49; -.
DR   PDBsum; 1J4A; -.
DR   ProteinModelPortal; P26297; -.
DR   SMR; P26297; -.
DR   STRING; 390333.Ldb0101; -.
DR   PRIDE; P26297; -.
DR   EnsemblBacteria; CAI96942; CAI96942; Ldb0101.
DR   GeneID; 4085369; -.
DR   KEGG; ldb:Ldb0101; -.
DR   PATRIC; fig|390333.13.peg.1571; -.
DR   eggNOG; ENOG4105C5I; Bacteria.
DR   eggNOG; COG1052; LUCA.
DR   HOGENOM; HOG000136695; -.
DR   KO; K03778; -.
DR   OMA; THKAYNR; -.
DR   BioCyc; LDEL390333:LDB_RS00400-MONOMER; -.
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; Complete proteome; Direct protein sequencing; NAD;
KW   Oxidoreductase; Reference proteome.
FT   INIT_MET      1      1       Removed.
FT   CHAIN         2    333       D-lactate dehydrogenase.
FT                                /FTId=PRO_0000075953.
FT   NP_BIND     156    157       NAD. {ECO:0000244|PDB:1J49,
FT                                ECO:0000269|PubMed:12054772}.
FT   NP_BIND     207    208       NAD. {ECO:0000269|PubMed:12054772}.
FT   NP_BIND     234    236       NAD. {ECO:0000305|PubMed:12054772}.
FT   ACT_SITE    236    236       {ECO:0000305|PubMed:9063466}.
FT   ACT_SITE    265    265       {ECO:0000305|PubMed:9063466}.
FT   ACT_SITE    297    297       Proton donor.
FT                                {ECO:0000305|PubMed:9063466}.
FT   BINDING     176    176       NAD. {ECO:0000244|PDB:1J49,
FT                                ECO:0000269|PubMed:12054772}.
FT   BINDING     213    213       NAD. {ECO:0000244|PDB:1J49,
FT                                ECO:0000269|PubMed:12054772}.
FT   BINDING     260    260       NAD. {ECO:0000244|PDB:1J49,
FT                                ECO:0000269|PubMed:12054772}.
FT   MUTAGEN     206    206       H->Q: Increase of activity.
FT                                {ECO:0000269|PubMed:9063466}.
FT   MUTAGEN     236    236       R->K: Decrease of activity.
FT                                {ECO:0000269|PubMed:9063466}.
FT   MUTAGEN     260    260       D->N: Decrease of activity.
FT                                {ECO:0000269|PubMed:9063466}.
FT   MUTAGEN     265    265       E->Q: Decrease of activity.
FT                                {ECO:0000269|PubMed:9063466}.
FT   MUTAGEN     297    297       H->Q: 90% loss of activity.
FT                                {ECO:0000269|PubMed:9063466}.
FT   CONFLICT     41     41       V -> A (in Ref. 2; AAA25246).
FT                                {ECO:0000305}.
FT   CONFLICT    117    117       R -> A (in Ref. 1; CAA42781).
FT                                {ECO:0000305}.
FT   CONFLICT    122    122       D -> A (in Ref. 2; AAA25246).
FT                                {ECO:0000305}.
FT   CONFLICT    152    152       I -> V (in Ref. 2; AAA25246).
FT                                {ECO:0000305}.
FT   CONFLICT    174    174       A -> T (in Ref. 1; CAA42781).
FT                                {ECO:0000305}.
FT   CONFLICT    220    220       E -> K (in Ref. 2; AAA25246).
FT                                {ECO:0000305}.
FT   CONFLICT    254    254       I -> V (in Ref. 2; AAA25246).
FT                                {ECO:0000305}.
FT   CONFLICT    268    268       I -> V (in Ref. 2; AAA25246).
FT                                {ECO:0000305}.
FT   CONFLICT    273    273       W -> R (in Ref. 2; AAA25246).
FT                                {ECO:0000305}.
FT   STRAND        3      6       {ECO:0000244|PDB:1J4A}.
FT   HELIX        11     13       {ECO:0000244|PDB:1J4A}.
FT   HELIX        14     22       {ECO:0000244|PDB:1J4A}.
FT   STRAND       27     31       {ECO:0000244|PDB:1J4A}.
FT   TURN         38     40       {ECO:0000244|PDB:1J4A}.
FT   HELIX        41     44       {ECO:0000244|PDB:1J4A}.
FT   STRAND       48     52       {ECO:0000244|PDB:1J4A}.
FT   HELIX        60     68       {ECO:0000244|PDB:1J4A}.
FT   STRAND       73     79       {ECO:0000244|PDB:1J4A}.
FT   HELIX        86     91       {ECO:0000244|PDB:1J4A}.
FT   STRAND       95     97       {ECO:0000244|PDB:1J4A}.
FT   HELIX       104    120       {ECO:0000244|PDB:1J4A}.
FT   HELIX       122    130       {ECO:0000244|PDB:1J4A}.
FT   HELIX       144    146       {ECO:0000244|PDB:1J4A}.
FT   STRAND      147    152       {ECO:0000244|PDB:1J4A}.
FT   HELIX       156    167       {ECO:0000244|PDB:1J4A}.
FT   STRAND      171    175       {ECO:0000244|PDB:1J4A}.
FT   HELIX       181    185       {ECO:0000244|PDB:1J4A}.
FT   HELIX       193    199       {ECO:0000244|PDB:1J4A}.
FT   STRAND      201    205       {ECO:0000244|PDB:1J4A}.
FT   HELIX       211    213       {ECO:0000244|PDB:1J4A}.
FT   HELIX       219    224       {ECO:0000244|PDB:1J4A}.
FT   STRAND      229    233       {ECO:0000244|PDB:1J4A}.
FT   HELIX       237    239       {ECO:0000244|PDB:1J4A}.
FT   HELIX       242    250       {ECO:0000244|PDB:1J4A}.
FT   STRAND      253    260       {ECO:0000244|PDB:1J4A}.
FT   TURN        266    270       {ECO:0000244|PDB:1J4A}.
FT   HELIX       281    288       {ECO:0000244|PDB:1J4A}.
FT   STRAND      292    294       {ECO:0000244|PDB:1J4A}.
FT   HELIX       303    321       {ECO:0000244|PDB:1J4A}.
FT   STRAND      327    329       {ECO:0000244|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
//
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