ID MDH_THETH Reviewed; 327 AA. AC P10584; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 13-SEP-2023, entry version 152. DE RecName: Full=Malate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_01517}; DE EC=1.1.1.37 {ECO:0000255|HAMAP-Rule:MF_01517}; GN Name=mdh {ECO:0000255|HAMAP-Rule:MF_01517}; OS Thermus thermophilus. OC Bacteria; Deinococcota; Deinococci; Thermales; Thermaceae; Thermus. OX NCBI_TaxID=274; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 1-37 AND RP 265-284. RC STRAIN=ATCC 33923 / DSM 674 / AT-62; RX PubMed=3771528; DOI=10.1016/s0021-9258(18)67000-0; RA Nishiyama M., Matsubara N., Yamamoto K., Iijima S., Uozumi T., Beppu T.; RT "Nucleotide sequence of the malate dehydrogenase gene of Thermus flavus and RT its mutation directing an increase in enzyme activity."; RL J. Biol. Chem. 261:14178-14183(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 33923 / DSM 674 / AT-62; RX PubMed=2034208; DOI=10.1007/bf00273580; RA Nishiyama M., Horinouchi S., Beppu T.; RT "Characterization of an operon encoding succinyl-CoA synthetase and malate RT dehydrogenase from Thermus flavus AT-62 and its expression in Escherichia RT coli."; RL Mol. Gen. Genet. 226:1-9(1991). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=B / NCIMB 11247; RX PubMed=2204576; DOI=10.1016/0378-1097(90)90093-6; RA Nicholls D.J., Sundaram T.K., Atkinson T., Minton N.P.; RT "Cloning and nucleotide sequences of the mdh and sucD genes from Thermus RT aquaticus B."; RL FEMS Microbiol. Lett. 58:7-14(1990). RN [4] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH NAD. RC STRAIN=ATCC 33923 / DSM 674 / AT-62; RX PubMed=8471603; DOI=10.1021/bi00066a010; RA Kelly C.A., Nishiyama M., Ohnishi Y., Beppu T., Birktoft J.J.; RT "Determinants of protein thermostability observed in the 1.9-A crystal RT structure of malate dehydrogenase from the thermophilic bacterium Thermus RT flavus."; RL Biochemistry 32:3913-3922(1993). RN [5] RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) IN COMPLEX WITH NADP. RX PubMed=16009341; DOI=10.1016/j.bbrc.2005.06.133; RA Tomita T., Fushinobu S., Kuzuyama T., Nishiyama M.; RT "Crystal structure of NAD-dependent malate dehydrogenase complexed with RT NADP(H)."; RL Biochem. Biophys. Res. Commun. 334:613-618(2005). RN [6] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS). RG RIKEN structural genomics initiative (RSGI); RT "Crystal structure of malate dehydrogenase from Thermus thermophilus HB8."; RL Submitted (OCT-2002) to the PDB data bank. CC -!- FUNCTION: Catalyzes the reversible oxidation of malate to oxaloacetate. CC {ECO:0000255|HAMAP-Rule:MF_01517}. 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 -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:16009341}. CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 2 family. CC {ECO:0000255|HAMAP-Rule:MF_01517, ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J02598; AAA27499.1; -; Genomic_DNA. DR EMBL; X54073; CAA38008.1; -; Genomic_DNA. DR EMBL; X56033; CAA39508.1; -; Genomic_DNA. DR RefSeq; WP_011172623.1; NZ_LR027517.1. DR PDB; 1BDM; X-ray; 1.80 A; A/B=1-327. DR PDB; 1BMD; X-ray; 1.90 A; A/B=1-327. DR PDB; 1IZ9; X-ray; 2.00 A; A/B=1-327. DR PDB; 1WZE; X-ray; 2.00 A; A/B=1-327. DR PDB; 1WZI; X-ray; 2.00 A; A/B=1-327. DR PDB; 1Y7T; X-ray; 1.65 A; A/B=1-327. DR PDB; 2CVQ; X-ray; 2.08 A; A/B=1-327. DR PDB; 4KDE; X-ray; 1.80 A; A/B=1-327. DR PDB; 4KDF; X-ray; 2.36 A; A/B/C/D=1-327. DR PDBsum; 1BDM; -. DR PDBsum; 1BMD; -. DR PDBsum; 1IZ9; -. DR PDBsum; 1WZE; -. DR PDBsum; 1WZI; -. DR PDBsum; 1Y7T; -. DR PDBsum; 2CVQ; -. DR PDBsum; 4KDE; -. DR PDBsum; 4KDF; -. DR AlphaFoldDB; P10584; -. DR SMR; P10584; -. DR BindingDB; P10584; -. DR ChEMBL; CHEMBL4255; -. DR DrugCentral; P10584; -. DR GeneID; 3168364; -. DR OMA; TKGMERG; -. DR BRENDA; 1.1.1.37; 2305. DR SABIO-RK; P10584; -. DR EvolutionaryTrace; P10584; -. 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 3D-structure; Direct protein sequencing; NAD; Oxidoreductase; KW Tricarboxylic acid cycle. FT CHAIN 1..327 FT /note="Malate dehydrogenase" FT /id="PRO_0000113400" FT ACT_SITE 187 FT /note="Proton acceptor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01517" FT BINDING 11..17 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01517, FT ECO:0000269|PubMed:16009341, ECO:0000269|PubMed:8471603" FT BINDING 92 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01517" FT BINDING 98 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01517" FT BINDING 105 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01517" FT BINDING 112 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01517, FT ECO:0000269|PubMed:16009341" FT BINDING 129..131 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01517, FT ECO:0000269|PubMed:16009341, ECO:0000269|PubMed:8471603" FT BINDING 131 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01517" FT BINDING 162 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01517" FT VARIANT 190 FT /note="T -> I (in strain: F428; produces a 2 to 3 times FT higher enzyme activity)" FT STRAND 5..11 FT /evidence="ECO:0007829|PDB:1Y7T" FT HELIX 15..25 FT /evidence="ECO:0007829|PDB:1Y7T" FT TURN 26..30 FT /evidence="ECO:0007829|PDB:1Y7T" FT STRAND 36..41 FT /evidence="ECO:0007829|PDB:1Y7T" FT HELIX 44..46 FT /evidence="ECO:0007829|PDB:1Y7T" FT HELIX 47..58 FT /evidence="ECO:0007829|PDB:1Y7T" FT TURN 59..61 FT /evidence="ECO:0007829|PDB:1Y7T" FT STRAND 65..72 FT /evidence="ECO:0007829|PDB:1Y7T" FT HELIX 74..77 FT /evidence="ECO:0007829|PDB:1Y7T" FT TURN 78..80 FT /evidence="ECO:0007829|PDB:1Y7T" FT STRAND 82..86 FT /evidence="ECO:0007829|PDB:1Y7T" FT HELIX 98..119 FT /evidence="ECO:0007829|PDB:1Y7T" FT STRAND 125..128 FT /evidence="ECO:0007829|PDB:1Y7T" FT STRAND 130..132 FT /evidence="ECO:0007829|PDB:1Y7T" FT HELIX 133..142 FT /evidence="ECO:0007829|PDB:1Y7T" FT HELIX 149..151 FT /evidence="ECO:0007829|PDB:1Y7T" FT STRAND 152..154 FT /evidence="ECO:0007829|PDB:1Y7T" FT HELIX 157..171 FT /evidence="ECO:0007829|PDB:1Y7T" FT HELIX 175..177 FT /evidence="ECO:0007829|PDB:1Y7T" FT STRAND 182..185 FT /evidence="ECO:0007829|PDB:1Y7T" FT STRAND 192..194 FT /evidence="ECO:0007829|PDB:1Y7T" FT HELIX 205..207 FT /evidence="ECO:0007829|PDB:1Y7T" FT HELIX 211..216 FT /evidence="ECO:0007829|PDB:1Y7T" FT HELIX 218..233 FT /evidence="ECO:0007829|PDB:1Y7T" FT HELIX 238..253 FT /evidence="ECO:0007829|PDB:1Y7T" FT STRAND 262..267 FT /evidence="ECO:0007829|PDB:1Y7T" FT HELIX 271..273 FT /evidence="ECO:0007829|PDB:1Y7T" FT STRAND 278..287 FT /evidence="ECO:0007829|PDB:1Y7T" FT STRAND 290..293 FT /evidence="ECO:0007829|PDB:1Y7T" FT HELIX 301..323 FT /evidence="ECO:0007829|PDB:1Y7T" SQ SEQUENCE 327 AA; 35426 MW; 31FA90DED2393DF2 CRC64; MKAPVRVAVT GAAGQIGYSL LFRIAAGEML GKDQPVILQL LEIPQAMKAL EGVVMELEDC AFPLLAGLEA TDDPKVAFKD ADYALLVGAA PRKAGMERRD LLQVNGKIFT EQGRALAEVA KKDVKVLVVG NPANTNALIA YKNAPGLNPR NFTAMTRLDH NRAKAQLAKK TGTGVDRIRR MTVWGNHSST MFPDLFHAEV DGRPALELVD MEWYEKVFIP TVAQRGAAII QARGASSAAS AANAAIEHIR DWALGTPEGD WVSMAVPSQG EYGIPEGIVY SFPVTAKDGA YRVVEGLEIN EFARKRMEIT AQELLDEMEQ VKALGLI //