MDH_METJA
ID MDH_METJA Reviewed; 313 AA.
AC Q60176;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=L-2-hydroxycarboxylate dehydrogenase (NAD(P)(+)) {ECO:0000305};
DE EC=1.1.1.375 {ECO:0000269|PubMed:10850983, ECO:0000269|PubMed:10998181, ECO:0000269|PubMed:19555779};
DE AltName: Full=MdhII {ECO:0000303|PubMed:10850983};
GN Name=mdh; Synonyms=mdhB; OrderedLocusNames=MJ0490;
OS Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM
OS 10045 / NBRC 100440) (Methanococcus jannaschii).
OC Archaea; Euryarchaeota; Methanomada group; Methanococci; Methanococcales;
OC Methanocaldococcaceae; Methanocaldococcus.
OX NCBI_TaxID=243232;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX PubMed=8688087; DOI=10.1126/science.273.5278.1058;
RA Bult C.J., White O., Olsen G.J., Zhou L., Fleischmann R.D., Sutton G.G.,
RA Blake J.A., FitzGerald L.M., Clayton R.A., Gocayne J.D., Kerlavage A.R.,
RA Dougherty B.A., Tomb J.-F., Adams M.D., Reich C.I., Overbeek R.,
RA Kirkness E.F., Weinstock K.G., Merrick J.M., Glodek A., Scott J.L.,
RA Geoghagen N.S.M., Weidman J.F., Fuhrmann J.L., Nguyen D., Utterback T.R.,
RA Kelley J.M., Peterson J.D., Sadow P.W., Hanna M.C., Cotton M.D.,
RA Roberts K.M., Hurst M.A., Kaine B.P., Borodovsky M., Klenk H.-P.,
RA Fraser C.M., Smith H.O., Woese C.R., Venter J.C.;
RT "Complete genome sequence of the methanogenic archaeon, Methanococcus
RT jannaschii.";
RL Science 273:1058-1073(1996).
RN [2]
RP FUNCTION AS MALATE/SULFOLACTATE DEHYDROGENASE, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10850983; DOI=10.1128/jb.182.13.3688-3692.2000;
RA Graupner M., Xu H., White R.H.;
RT "Identification of an archaeal 2-hydroxy acid dehydrogenase catalyzing
RT reactions involved in coenzyme biosynthesis in methanoarchaea.";
RL J. Bacteriol. 182:3688-3692(2000).
RN [3]
RP FUNCTION AS A MALATE DEHYDROGENASE, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND SUBUNIT.
RX PubMed=10998181; DOI=10.1046/j.1365-2958.2000.02113.x;
RA Madern D.;
RT "The putative L-lactate dehydrogenase from Methanococcus jannaschii is an
RT NADPH-dependent L-malate dehydrogenase.";
RL Mol. Microbiol. 37:1515-1520(2000).
RN [4]
RP SUBUNIT.
RX PubMed=11513609; DOI=10.1021/bi010168c;
RA Madern D., Ebel C., Dale H.A., Lien T., Steen I.H., Birkeland N.-K.,
RA Zaccai G.;
RT "Differences in the oligomeric states of the LDH-like L-MalDH from the
RT hyperthermophilic archaea Methanococcus jannaschii and Archaeoglobus
RT fulgidus.";
RL Biochemistry 40:10310-10316(2001).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=19555779; DOI=10.1016/j.bbapap.2009.06.014;
RA Kawakami R., Sakuraba H., Goda S., Tsuge H., Ohshima T.;
RT "Refolding, characterization and crystal structure of (S)-malate
RT dehydrogenase from the hyperthermophilic archaeon Aeropyrum pernix.";
RL Biochim. Biophys. Acta 1794:1496-1504(2009).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH NADP, AND SUBUNIT.
RX PubMed=11292347; DOI=10.1006/jmbi.2001.4532;
RA Lee B.I., Chang C., Cho S.-J., Eom S.H., Kim K.K., Yu Y.G., Suh S.W.;
RT "Crystal structure of the MJ0490 gene product of the hyperthermophilic
RT archaebacterium Methanococcus jannaschii, a novel member of the
RT lactate/malate family of dehydrogenases.";
RL J. Mol. Biol. 307:1351-1362(2001).
CC -!- FUNCTION: Catalyzes the reversible oxidation of (S)-malate and (S)-
CC sulfolactate to oxaloacetate and sulfopyruvate, respectively. Can use
CC both NADH and NADPH, although activity is higher with NADPH. Oxidation
CC of (S)-sulfolactate is observed only in the presence of NADP(+). Can
CC also oxidize tartrate. Cannot reduce pyruvate, nor alpha-ketoglutarate.
CC {ECO:0000269|PubMed:10850983, ECO:0000269|PubMed:10998181,
CC ECO:0000269|PubMed:19555779}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (2S)-2-hydroxycarboxylate + NAD(+) = a 2-oxocarboxylate +
CC H(+) + NADH; Xref=Rhea:RHEA:34555, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:35179, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:58123; EC=1.1.1.375;
CC Evidence={ECO:0000269|PubMed:10850983, ECO:0000269|PubMed:10998181,
CC ECO:0000269|PubMed:19555779};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (2S)-2-hydroxycarboxylate + NADP(+) = a 2-oxocarboxylate +
CC H(+) + NADPH; Xref=Rhea:RHEA:42768, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:35179, ChEBI:CHEBI:57783, ChEBI:CHEBI:58123,
CC ChEBI:CHEBI:58349; EC=1.1.1.375;
CC Evidence={ECO:0000269|PubMed:10850983, ECO:0000269|PubMed:10998181,
CC ECO:0000269|PubMed:19555779};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.15 mM for (S)-malate (in the presence of NAD(+))
CC {ECO:0000269|PubMed:10850983};
CC KM=0.41 mM for (S)-malate (in the presence of NAD(+))
CC {ECO:0000269|PubMed:19555779};
CC KM=0.025 mM for (S)-malate (in the presence of NADP(+))
CC {ECO:0000269|PubMed:10850983};
CC KM=0.084 mM for (S)-malate (in the presence of NADP(+))
CC {ECO:0000269|PubMed:19555779};
CC KM=4.6 mM for (S)-sulfolactate (in the presence of NADP(+))
CC {ECO:0000269|PubMed:10850983};
CC KM=11 mM for (2S,3S)-tartrate (in the presence of NAD(+))
CC {ECO:0000269|PubMed:19555779};
CC KM=5.1 mM for (2S,3S)-tartrate (in the presence of NADP(+))
CC {ECO:0000269|PubMed:19555779};
CC KM=0.25 mM for oxaloacetate (in the presence of NADH)
CC {ECO:0000269|PubMed:10850983};
CC KM=0.30 mM for oxaloacetate (in the presence of NADPH)
CC {ECO:0000269|PubMed:10850983};
CC KM=1.3 mM for sulfopyruvate (in the presence of NADH)
CC {ECO:0000269|PubMed:10850983};
CC KM=0.19 mM for sulfopyruvate (in the presence of NADPH)
CC {ECO:0000269|PubMed:10850983};
CC KM=0.14 mM for NADH {ECO:0000269|PubMed:10998181};
CC KM=0.02 mM for NADPH {ECO:0000269|PubMed:10998181};
CC Vmax=0.6 umol/min/mg enzyme toward (S)-malate (in the presence of
CC NAD(+)) {ECO:0000269|PubMed:10850983};
CC Vmax=3 umol/min/mg enzyme toward (S)-malate (in the presence of
CC NADP(+)) {ECO:0000269|PubMed:10850983};
CC Vmax=3 umol/min/mg enzyme toward (S)-sulfolactate (in the presence of
CC NADP(+)) {ECO:0000269|PubMed:10850983};
CC Vmax=29 umol/min/mg enzyme toward oxaloacetate (in the presence of
CC NADH) {ECO:0000269|PubMed:10850983};
CC Vmax=49 umol/min/mg enzyme toward oxaloacetate (in the presence of
CC NADPH) {ECO:0000269|PubMed:10850983};
CC Vmax=43 umol/min/mg enzyme toward sulfopyruvate (in the presence of
CC NADH) {ECO:0000269|PubMed:10850983};
CC Vmax=69 umol/min/mg enzyme toward sulfopyruvate (in the presence of
CC NADPH) {ECO:0000269|PubMed:10850983};
CC Note=kcat is 0.33 sec(-1) for NAD-dependent malate oxidation. kcat is
CC 0.069 sec(-1) for NADP-dependent malate oxidation.
CC {ECO:0000269|PubMed:19555779};
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:10998181,
CC ECO:0000269|PubMed:11292347, ECO:0000269|PubMed:11513609}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. {ECO:0000305}.
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DR EMBL; L77117; AAB98481.1; -; Genomic_DNA.
DR PIR; B64361; B64361.
DR RefSeq; WP_010869991.1; NC_000909.1.
DR PDB; 1HYE; X-ray; 1.90 A; A=1-313.
DR PDB; 1HYG; X-ray; 2.80 A; A/B=1-313.
DR PDBsum; 1HYE; -.
DR PDBsum; 1HYG; -.
DR AlphaFoldDB; Q60176; -.
DR SMR; Q60176; -.
DR STRING; 243232.MJ_0490; -.
DR EnsemblBacteria; AAB98481; AAB98481; MJ_0490.
DR GeneID; 1451352; -.
DR KEGG; mja:MJ_0490; -.
DR eggNOG; arCOG00246; Archaea.
DR HOGENOM; CLU_045401_2_2_2; -.
DR InParanoid; Q60176; -.
DR OMA; ASCAEYI; -.
DR OrthoDB; 69007at2157; -.
DR PhylomeDB; Q60176; -.
DR BioCyc; MetaCyc:MON-18778; -.
DR BRENDA; 1.1.1.375; 3260.
DR SABIO-RK; Q60176; -.
DR EvolutionaryTrace; Q60176; -.
DR Proteomes; UP000000805; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0102443; F:L-2-hydroxycarboxylate dehydrogenase (NAD+) activity; IEA:RHEA.
DR GO; GO:0004459; F:L-lactate dehydrogenase activity; IEA:InterPro.
DR GO; GO:0019752; P:carboxylic acid metabolic process; IEA:InterPro.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR Gene3D; 3.90.110.10; -; 1.
DR InterPro; IPR001557; L-lactate/malate_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.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; NAD; NADP; Oxidoreductase; Reference proteome;
KW Tricarboxylic acid cycle.
FT CHAIN 1..313
FT /note="L-2-hydroxycarboxylate dehydrogenase (NAD(P)(+))"
FT /id="PRO_0000113485"
FT ACT_SITE 178
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P61889"
FT BINDING 7..13
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11292347"
FT BINDING 34..37
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11292347"
FT BINDING 86
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P61889"
FT BINDING 92
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P61889"
FT BINDING 99
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11292347"
FT BINDING 121..123
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11292347"
FT BINDING 123
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P61889"
FT BINDING 154
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P61889"
FT STRAND 2..6
FT /evidence="ECO:0007829|PDB:1HYE"
FT TURN 7..9
FT /evidence="ECO:0007829|PDB:1HYE"
FT HELIX 11..21
FT /evidence="ECO:0007829|PDB:1HYE"
FT STRAND 28..33
FT /evidence="ECO:0007829|PDB:1HYE"
FT HELIX 35..37
FT /evidence="ECO:0007829|PDB:1HYE"
FT HELIX 38..52
FT /evidence="ECO:0007829|PDB:1HYE"
FT STRAND 60..65
FT /evidence="ECO:0007829|PDB:1HYE"
FT HELIX 69..72
FT /evidence="ECO:0007829|PDB:1HYE"
FT STRAND 76..80
FT /evidence="ECO:0007829|PDB:1HYE"
FT HELIX 92..113
FT /evidence="ECO:0007829|PDB:1HYE"
FT STRAND 117..120
FT /evidence="ECO:0007829|PDB:1HYE"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:1HYE"
FT HELIX 125..136
FT /evidence="ECO:0007829|PDB:1HYE"
FT STRAND 142..145
FT /evidence="ECO:0007829|PDB:1HYE"
FT HELIX 149..163
FT /evidence="ECO:0007829|PDB:1HYE"
FT HELIX 167..169
FT /evidence="ECO:0007829|PDB:1HYE"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:1HYE"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:1HYE"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:1HYE"
FT HELIX 196..198
FT /evidence="ECO:0007829|PDB:1HYE"
FT HELIX 200..204
FT /evidence="ECO:0007829|PDB:1HYE"
FT HELIX 207..217
FT /evidence="ECO:0007829|PDB:1HYE"
FT HELIX 219..222
FT /evidence="ECO:0007829|PDB:1HYG"
FT STRAND 225..227
FT /evidence="ECO:0007829|PDB:1HYG"
FT HELIX 232..244
FT /evidence="ECO:0007829|PDB:1HYE"
FT STRAND 249..263
FT /evidence="ECO:0007829|PDB:1HYE"
FT STRAND 265..276
FT /evidence="ECO:0007829|PDB:1HYE"
FT STRAND 279..283
FT /evidence="ECO:0007829|PDB:1HYE"
FT HELIX 290..310
FT /evidence="ECO:0007829|PDB:1HYE"
SQ SEQUENCE 313 AA; 34609 MW; A7C0DB67C50151CC CRC64;
MKVTIIGASG RVGSATALLL AKEPFMKDLV LIGREHSINK LEGLREDIYD ALAGTRSDAN
IYVESDENLR IIDESDVVII TSGVPRKEGM SRMDLAKTNA KIVGKYAKKI AEICDTKIFV
ITNPVDVMTY KALVDSKFER NQVFGLGTHL DSLRFKVAIA KFFGVHIDEV RTRIIGEHGD
SMVPLLSATS IGGIPIQKFE RFKELPIDEI IEDVKTKGEQ IIRLKGGSEF GPAAAILNVV
RCIVNNEKRL LTLSAYVDGE FDGIRDVCIG VPVKIGRDGI EEVVSIELDK DEIIAFRKSA
EIIKKYCEEV KNL
