ID   MDH_CHLAA               Reviewed;         309 AA.
AC   P80040; A9WH38;
DT   01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT   18-MAR-2008, sequence version 3.
DT   27-MAR-2024, entry version 159.
DE   RecName: Full=Malate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_00487};
DE            EC=1.1.1.37 {ECO:0000255|HAMAP-Rule:MF_00487};
GN   Name=mdh {ECO:0000255|HAMAP-Rule:MF_00487};
GN   OrderedLocusNames=Caur_0900;
OS   Chloroflexus aurantiacus (strain ATCC 29366 / DSM 635 / J-10-fl).
OC   Bacteria; Chloroflexota; Chloroflexia; Chloroflexales; Chloroflexineae;
OC   Chloroflexaceae; Chloroflexus.
OX   NCBI_TaxID=324602;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8661927; DOI=10.1007/s002030050337;
RA   Synstad B., Emmerhoff O., Sirevag R.;
RT   "Malate dehydrogenase from the green gliding bacterium Chloroflexus
RT   aurantiacus is phylogenetically related to lactic dehydrogenases.";
RL   Arch. Microbiol. 165:346-353(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 29366 / DSM 635 / J-10-fl;
RX   PubMed=21714912; DOI=10.1186/1471-2164-12-334;
RA   Tang K.H., Barry K., Chertkov O., Dalin E., Han C.S., Hauser L.J.,
RA   Honchak B.M., Karbach L.E., Land M.L., Lapidus A., Larimer F.W.,
RA   Mikhailova N., Pitluck S., Pierson B.K., Blankenship R.E.;
RT   "Complete genome sequence of the filamentous anoxygenic phototrophic
RT   bacterium Chloroflexus aurantiacus.";
RL   BMC Genomics 12:334-334(2011).
RN   [3]
RP   PROTEIN SEQUENCE OF 1-35, AND SUBUNIT.
RX   PubMed=3133356; DOI=10.1128/jb.170.7.2947-2953.1988;
RA   Rolstad A.K., Howland E., Sirevag R.;
RT   "Malate dehydrogenase from the thermophilic green bacterium Chloroflexus
RT   aurantiacus: purification, molecular weight, amino acid composition, and
RT   partial amino acid sequence.";
RL   J. Bacteriol. 170:2947-2953(1988).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 11-306 IN COMPLEX WITH NAD, AND
RP   SUBUNIT.
RX   PubMed=12054817; DOI=10.1016/s0022-2836(02)00050-5;
RA   Dalhus B., Saarinen M., Sauer U.H., Eklund P., Johansson K., Karlsson A.,
RA   Ramaswamy S., Bjoerk A., Synstad B., Naterstad K., Sirevaag R., Eklund H.;
RT   "Structural basis for thermophilic protein stability: structures of
RT   thermophilic and mesophilic malate dehydrogenases.";
RL   J. Mol. Biol. 318:707-721(2002).
RN   [5]
RP   X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF MUTANT CYS-187 IN COMPLEX WITH
RP   NAD AND SUBSTRATE ANALOG, AND SUBUNIT.
RX   PubMed=14636605; DOI=10.1016/j.jmb.2003.10.006;
RA   Bjoerk A., Dalhus B., Mantzilas D., Eijsink V.G.H., Sirevaag R.;
RT   "Stabilization of a tetrameric malate dehydrogenase by introduction of a
RT   disulfide bridge at the dimer-dimer interface.";
RL   J. Mol. Biol. 334:811-821(2003).
CC   -!- FUNCTION: Catalyzes the reversible oxidation of malate to oxaloacetate.
CC       {ECO:0000255|HAMAP-Rule:MF_00487}.
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_00487};
CC   -!- SUBUNIT: Homotetramer (active enzyme); homodimer and homotrimer at
CC       temperatures lower than 55 degrees Celsius (inactive forms).
CC       {ECO:0000269|PubMed:12054817, ECO:0000269|PubMed:14636605,
CC       ECO:0000269|PubMed:3133356}.
CC   -!- SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 3 family.
CC       {ECO:0000255|HAMAP-Rule:MF_00487}.
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DR   EMBL; X89038; CAA61436.1; -; Genomic_DNA.
DR   EMBL; CP000909; ABY34133.1; -; Genomic_DNA.
DR   RefSeq; WP_012256789.1; NC_010175.1.
DR   RefSeq; YP_001634522.1; NC_010175.1.
DR   PDB; 1GUY; X-ray; 2.20 A; A/C=1-309.
DR   PDB; 1UR5; X-ray; 1.75 A; A/C=1-309.
DR   PDB; 1UXG; X-ray; 1.90 A; A/B=1-309.
DR   PDB; 1UXH; X-ray; 2.10 A; A/B=1-309.
DR   PDB; 1UXI; X-ray; 2.10 A; A/B=1-309.
DR   PDB; 1UXJ; X-ray; 1.75 A; A/C=1-309.
DR   PDB; 1UXK; X-ray; 1.80 A; A/C=1-309.
DR   PDB; 4CL3; X-ray; 1.70 A; A/D=1-309.
DR   PDBsum; 1GUY; -.
DR   PDBsum; 1UR5; -.
DR   PDBsum; 1UXG; -.
DR   PDBsum; 1UXH; -.
DR   PDBsum; 1UXI; -.
DR   PDBsum; 1UXJ; -.
DR   PDBsum; 1UXK; -.
DR   PDBsum; 4CL3; -.
DR   AlphaFoldDB; P80040; -.
DR   SMR; P80040; -.
DR   STRING; 324602.Caur_0900; -.
DR   DrugBank; DB01677; Fumaric acid.
DR   EnsemblBacteria; ABY34133; ABY34133; Caur_0900.
DR   KEGG; cau:Caur_0900; -.
DR   PATRIC; fig|324602.8.peg.1031; -.
DR   eggNOG; COG0039; Bacteria.
DR   HOGENOM; CLU_045401_2_1_0; -.
DR   InParanoid; P80040; -.
DR   BRENDA; 1.1.1.37; 1352.
DR   EvolutionaryTrace; P80040; -.
DR   Proteomes; UP000002008; Chromosome.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0030060; F:L-malate dehydrogenase activity; IBA:GO_Central.
DR   GO; GO:0019752; P:carboxylic acid metabolic process; IEA:InterPro.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-UniRule.
DR   CDD; cd01339; LDH-like_MDH; 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_00487; Malate_dehydrog_3; 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; IPR011275; Malate_DH_type3.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   NCBIfam; TIGR01763; MalateDH_bact; 1.
DR   PANTHER; PTHR43128; L-2-HYDROXYCARBOXYLATE DEHYDROGENASE (NAD(P)(+)); 1.
DR   PANTHER; PTHR43128:SF34; L-LACTATE DEHYDROGENASE; 1.
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; SSF56327; LDH C-terminal domain-like; 1.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; NAD; Oxidoreductase;
KW   Reference proteome; Tricarboxylic acid cycle.
FT   CHAIN           1..309
FT                   /note="Malate dehydrogenase"
FT                   /id="PRO_0000113447"
FT   ACT_SITE        175
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P61889, ECO:0000255|HAMAP-
FT                   Rule:MF_00487"
FT   BINDING         9..14
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00487,
FT                   ECO:0000269|PubMed:12054817, ECO:0000269|PubMed:14636605"
FT   BINDING         33
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00487,
FT                   ECO:0000269|PubMed:12054817, ECO:0000269|PubMed:14636605"
FT   BINDING         82
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P61889, ECO:0000255|HAMAP-
FT                   Rule:MF_00487"
FT   BINDING         88
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P61889, ECO:0000255|HAMAP-
FT                   Rule:MF_00487"
FT   BINDING         95
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P61889, ECO:0000255|HAMAP-
FT                   Rule:MF_00487"
FT   BINDING         118..120
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00487,
FT                   ECO:0000269|PubMed:12054817, ECO:0000269|PubMed:14636605"
FT   BINDING         120
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P61889, ECO:0000255|HAMAP-
FT                   Rule:MF_00487"
FT   BINDING         151
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P61889, ECO:0000255|HAMAP-
FT                   Rule:MF_00487"
FT   MUTAGEN         187
FT                   /note="T->C: Forms an intersubunit disulfide bridge, which
FT                   makes the enzyme more resistant to thermal denaturation.
FT                   The mutation does not alter the quaternary structure of the
FT                   enzyme."
FT   CONFLICT        34
FT                   /note="F -> I (in Ref. 1; CAA61436 and 3)"
FT                   /evidence="ECO:0000305"
FT   STRAND          4..8
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   HELIX           12..23
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   STRAND          27..32
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   STRAND          34..37
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   HELIX           38..47
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   HELIX           50..53
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   STRAND          59..63
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   HELIX           65..68
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   STRAND          72..76
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   HELIX           90..106
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   HELIX           107..109
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   STRAND          114..117
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   STRAND          119..121
FT                   /evidence="ECO:0007829|PDB:1UXJ"
FT   HELIX           122..133
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   HELIX           137..139
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   STRAND          140..142
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   HELIX           145..160
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   HELIX           164..166
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   STRAND          167..169
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   STRAND          172..175
FT                   /evidence="ECO:0007829|PDB:1UXK"
FT   HELIX           176..178
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   HELIX           183..185
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   STRAND          186..188
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   HELIX           193..195
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   HELIX           199..210
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   HELIX           212..220
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   STRAND          221..223
FT                   /evidence="ECO:0007829|PDB:1UXJ"
FT   HELIX           227..241
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   STRAND          246..256
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   HELIX           257..259
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   STRAND          261..272
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   STRAND          275..279
FT                   /evidence="ECO:0007829|PDB:1UR5"
FT   HELIX           286..306
FT                   /evidence="ECO:0007829|PDB:1UR5"
SQ   SEQUENCE   309 AA;  32751 MW;  AE1BACC5D5B36331 CRC64;
     MRKKISIIGA GFVGSTTAHW LAAKELGDIV LLDFVEGVPQ GKALDLYEAS PIEGFDVRVT
     GTNNYADTAN SDVIVVTSGA PRKPGMSRED LIKVNADITR ACISQAAPLS PNAVIIMVNN
     PLDAMTYLAA EVSGFPKERV IGQAGVLDAA RYRTFIAMEA GVSVEDVQAM LMGGHGDEMV
     PLPRFSTISG IPVSEFIAPD RLAQIVERTR KGGGEIVNLL KTGSAYYAPA AATAQMVEAV
     LKDKKRVMPV AAYLTGQYGL NDIYFGVPVI LGAGGVEKIL ELPLNEEEMA LLNASAKAVR
     ATLDTLKSL
//