ID   MDH_STRAW               Reviewed;         329 AA.
AC   Q82HS2;
DT   07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2003, sequence version 1.
DT   27-MAR-2024, entry version 129.
DE   RecName: Full=Malate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_01517, ECO:0000303|PubMed:20845078};
DE            EC=1.1.1.37 {ECO:0000255|HAMAP-Rule:MF_01517, ECO:0000269|PubMed:20845078};
GN   Name=mdh {ECO:0000255|HAMAP-Rule:MF_01517};
GN   OrderedLocusNames=SAV_3436;
OS   Streptomyces avermitilis (strain ATCC 31267 / DSM 46492 / JCM 5070 / NBRC
OS   14893 / NCIMB 12804 / NRRL 8165 / MA-4680).
OC   Bacteria; Actinomycetota; Actinomycetes; Kitasatosporales;
OC   Streptomycetaceae; Streptomyces.
OX   NCBI_TaxID=227882;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 31267 / DSM 46492 / JCM 5070 / NBRC 14893 / NCIMB 12804 /
RC   NRRL 8165 / MA-4680;
RX   PubMed=11572948; DOI=10.1073/pnas.211433198;
RA   Omura S., Ikeda H., Ishikawa J., Hanamoto A., Takahashi C., Shinose M.,
RA   Takahashi Y., Horikawa H., Nakazawa H., Osonoe T., Kikuchi H., Shiba T.,
RA   Sakaki Y., Hattori M.;
RT   "Genome sequence of an industrial microorganism Streptomyces avermitilis:
RT   deducing the ability of producing secondary metabolites.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:12215-12220(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 31267 / DSM 46492 / JCM 5070 / NBRC 14893 / NCIMB 12804 /
RC   NRRL 8165 / MA-4680;
RX   PubMed=12692562; DOI=10.1038/nbt820;
RA   Ikeda H., Ishikawa J., Hanamoto A., Shinose M., Kikuchi H., Shiba T.,
RA   Sakaki Y., Hattori M., Omura S.;
RT   "Complete genome sequence and comparative analysis of the industrial
RT   microorganism Streptomyces avermitilis.";
RL   Nat. Biotechnol. 21:526-531(2003).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP   PROPERTIES.
RC   STRAIN=ATCC 31267 / DSM 46492 / JCM 5070 / NBRC 14893 / NCIMB 12804 /
RC   NRRL 8165 / MA-4680;
RX   PubMed=20845078; DOI=10.1007/s11033-010-0273-1;
RA   Wang Z.D., Wang B.J., Ge Y.D., Pan W., Wang J., Xu L., Liu A.M., Zhu G.P.;
RT   "Expression and identification of a thermostable malate dehydrogenase from
RT   multicellular prokaryote Streptomyces avermitilis MA-4680.";
RL   Mol. Biol. Rep. 38:1629-1636(2011).
CC   -!- FUNCTION: Catalyzes the reversible oxidation of malate to oxaloacetate.
CC       Exhibits remarkably higher catalytic efficiency for oxaloacetate
CC       reduction than for malate oxidation in vitro. Highly specific for
CC       NAD(H). Can also use NADPH for oxaloacetate reduction, but catalytic
CC       efficiency is 97-fold higher with NADH. No activity detected with
CC       NADP(+) and malate. {ECO:0000269|PubMed:20845078}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(S)-malate + NAD(+) = H(+) + NADH + oxaloacetate;
CC         Xref=Rhea:RHEA:21432, ChEBI:CHEBI:15378, ChEBI:CHEBI:15589,
CC         ChEBI:CHEBI:16452, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.37;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_01517,
CC         ECO:0000269|PubMed:20845078};
CC   -!- ACTIVITY REGULATION: Strongly inhibited by Hg(2+) and Zn(2+). Activated
CC       by Na(+), NH(4)(+), Ca(2+), Cu(2+) and Mg(2+).
CC       {ECO:0000269|PubMed:20845078}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=75.5 uM for oxaloacetate (in the presence of NADH)
CC         {ECO:0000269|PubMed:20845078};
CC         KM=433.6 uM for oxaloacetate (in the presence of NADPH)
CC         {ECO:0000269|PubMed:20845078};
CC         KM=36.8 uM for NADH {ECO:0000269|PubMed:20845078};
CC         KM=374.1 uM for NADPH {ECO:0000269|PubMed:20845078};
CC         KM=386 uM for malate {ECO:0000269|PubMed:20845078};
CC         KM=592 uM for NAD(+) {ECO:0000269|PubMed:20845078};
CC         Note=kcat is 1181.6 sec(-1) for NADH-dependent reduction of
CC         oxaloacetate. kcat is 67.4 sec(-1) for NADPH-dependent reduction of
CC         oxaloacetate. kcat is 4.88 sec(-1) for NAD(+)-dependent oxidation of
CC         malate. {ECO:0000269|PubMed:20845078};
CC       pH dependence:
CC         Optimum pH is 8.0. {ECO:0000269|PubMed:20845078};
CC       Temperature dependence:
CC         Optimum temperature is 42 degrees Celsius.
CC         {ECO:0000269|PubMed:20845078};
CC   -!- SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 2 family.
CC       {ECO:0000255|HAMAP-Rule:MF_01517}.
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DR   EMBL; BA000030; BAC71148.1; -; Genomic_DNA.
DR   RefSeq; WP_010984867.1; NZ_JZJK01000090.1.
DR   AlphaFoldDB; Q82HS2; -.
DR   SMR; Q82HS2; -.
DR   KEGG; sma:SAVERM_3436; -.
DR   eggNOG; COG0039; Bacteria.
DR   HOGENOM; CLU_040727_2_0_11; -.
DR   OrthoDB; 9802969at2; -.
DR   Proteomes; UP000000428; Chromosome.
DR   GO; GO:0030060; F:L-malate dehydrogenase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0006108; P:malate metabolic process; IEA:InterPro.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-UniRule.
DR   CDD; cd01338; MDH_choloroplast_like; 1.
DR   Gene3D; 3.90.110.10; Lactate dehydrogenase/glycoside hydrolase, family 4, C-terminal; 1.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR   HAMAP; MF_01517; Malate_dehydrog_2; 1.
DR   InterPro; IPR001557; L-lactate/malate_DH.
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; IPR001252; Malate_DH_AS.
DR   InterPro; IPR010945; Malate_DH_type2.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   NCBIfam; TIGR01759; MalateDH-SF1; 1.
DR   PANTHER; PTHR23382; MALATE DEHYDROGENASE; 1.
DR   PANTHER; PTHR23382:SF0; MALATE DEHYDROGENASE 2, MITOCHONDRIAL-RELATED; 1.
DR   Pfam; PF02866; Ldh_1_C; 1.
DR   Pfam; PF00056; Ldh_1_N; 1.
DR   PIRSF; PIRSF000102; Lac_mal_DH; 1.
DR   SUPFAM; SSF56327; LDH C-terminal domain-like; 1.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   PROSITE; PS00068; MDH; 1.
PE   1: Evidence at protein level;
KW   NAD; Oxidoreductase; Reference proteome; Tricarboxylic acid cycle.
FT   CHAIN           1..329
FT                   /note="Malate dehydrogenase"
FT                   /id="PRO_0000113393"
FT   ACT_SITE        188
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01517"
FT   BINDING         12..18
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01517"
FT   BINDING         93
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01517"
FT   BINDING         99
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01517"
FT   BINDING         106
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01517"
FT   BINDING         113
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01517"
FT   BINDING         130..132
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01517"
FT   BINDING         132
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01517"
FT   BINDING         163
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01517"
SQ   SEQUENCE   329 AA;  34689 MW;  D68E4B4720651655 CRC64;
     MTRTPVNVTV TGAAGQIGYA LLFRIASGQL LGADVPVKLR LLEITPALKA AEGTAMELDD
     CAFPLLQGID ITDDPNVAFD GTNVGLLVGA RPRTKGMERG DLLSANGGIF KPQGKAINDN
     AADDVKILVV GNPANTNALI AQAAAPDVPA ERFTAMTRLD HNRALTQLAK KTGSTVADIK
     RLTIWGNHSA TQYPDIFHAS VAGKNAAEVV NDEKWLAEDF IPTVAKRGAA IIEARGASSA
     ASAANAAIDH VYTWVNGTAD GDWTSMGIPS DGSYGVPEGL ISSFPVTTKD GRYEIVQGLE
     INEFSRARID ASVKELEEER EAVRALGLI
//