ID MDH_AERPE Reviewed; 308 AA. AC Q9YEA1; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 26-JUN-2007, sequence version 2. DT 27-MAR-2024, entry version 140. DE RecName: Full=Malate dehydrogenase {ECO:0000303|PubMed:19555779}; DE EC=1.1.1.299 {ECO:0000269|PubMed:19555779}; GN Name=mdh; OrderedLocusNames=APE_0672.1; OS Aeropyrum pernix (strain ATCC 700893 / DSM 11879 / JCM 9820 / NBRC 100138 / OS K1). OC Archaea; Thermoproteota; Thermoprotei; Desulfurococcales; OC Desulfurococcaceae; Aeropyrum. OX NCBI_TaxID=272557; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 700893 / DSM 11879 / JCM 9820 / NBRC 100138 / K1; RX PubMed=10382966; DOI=10.1093/dnares/6.2.83; RA Kawarabayasi Y., Hino Y., Horikawa H., Yamazaki S., Haikawa Y., Jin-no K., RA Takahashi M., Sekine M., Baba S., Ankai A., Kosugi H., Hosoyama A., RA Fukui S., Nagai Y., Nishijima K., Nakazawa H., Takamiya M., Masuda S., RA Funahashi T., Tanaka T., Kudoh Y., Yamazaki J., Kushida N., Oguchi A., RA Aoki K., Kubota K., Nakamura Y., Nomura N., Sako Y., Kikuchi H.; RT "Complete genome sequence of an aerobic hyper-thermophilic crenarchaeon, RT Aeropyrum pernix K1."; RL DNA Res. 6:83-101(1999). RN [2] RP X-RAY CRYSTALLOGRAPHY (2.87 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY, RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT. 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). CC -!- FUNCTION: Catalyzes the reversible oxidation of malate to oxaloacetate. CC Can also oxidize tartrate. Can utilize both NAD and NADP. Catalytic CC efficiency for malate oxidation is 3-fold higher with NADP. CC {ECO:0000269|PubMed:19555779}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(S)-malate + NADP(+) = H(+) + NADPH + oxaloacetate; CC Xref=Rhea:RHEA:10824, ChEBI:CHEBI:15378, ChEBI:CHEBI:15589, CC ChEBI:CHEBI:16452, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC EC=1.1.1.299; Evidence={ECO:0000269|PubMed:19555779}; 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; CC EC=1.1.1.299; Evidence={ECO:0000269|PubMed:19555779}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.12 mM for S-malate (in the presence of NAD) CC {ECO:0000269|PubMed:19555779}; CC KM=0.019 mM for S-malate (in the presence of NADP) CC {ECO:0000269|PubMed:19555779}; CC KM=1.2 mM for (2S,3S)-tartrate (in the presence of NAD) CC {ECO:0000269|PubMed:19555779}; CC KM=23 mM for (2S,3S)-tartrate (in the presence of NADP) CC {ECO:0000269|PubMed:19555779}; CC KM=0.2 mM for (2S,3R)-tartrate (in the presence of NAD) CC {ECO:0000269|PubMed:19555779}; CC KM=5.8 mM for (2S,3R)-tartrate (in the presence of NADP) CC {ECO:0000269|PubMed:19555779}; CC KM=0.87 mM for NAD (in the presence of malate) CC {ECO:0000269|PubMed:19555779}; CC KM=0.0076 mM for NADP (in the presence of malate) CC {ECO:0000269|PubMed:19555779}; CC Note=kcat is 2.6 sec(-1) for NAD-dependent malate oxidation. kcat is CC 1.4 sec(-1) for NADP-dependent malate oxidation. CC {ECO:0000269|PubMed:19555779}; CC pH dependence: CC Optimum pH is 11 for malate oxidation. {ECO:0000269|PubMed:19555779}; CC Temperature dependence: CC Optimum temperature is 95 degrees Celsius. CC {ECO:0000269|PubMed:19555779}; CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:19555779}. CC -!- MISCELLANEOUS: Ala at position 30 is responsible for coenzyme CC specificity. Asp or Glu is present at this position in most NAD- CC specific enzymes. The next residue, Arg, is important for NADP binding. CC {ECO:0000305|PubMed:19555779}. CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. {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; BA000002; BAA79645.2; -; Genomic_DNA. DR PIR; E72655; E72655. DR PDB; 2D4A; X-ray; 2.87 A; A/B/C/D=1-308. DR PDBsum; 2D4A; -. DR AlphaFoldDB; Q9YEA1; -. DR SMR; Q9YEA1; -. DR STRING; 272557.APE_0672.1; -. DR EnsemblBacteria; BAA79645; BAA79645; APE_0672.1. DR KEGG; ape:APE_0672.1; -. DR PATRIC; fig|272557.25.peg.482; -. DR eggNOG; arCOG00246; Archaea. DR BRENDA; 1.1.1.82; 171. DR EvolutionaryTrace; Q9YEA1; -. DR Proteomes; UP000002518; Chromosome. DR GO; GO:0030060; F:L-malate dehydrogenase activity; IEA:RHEA. DR GO; GO:0046554; F:malate dehydrogenase (NADP+) activity; IEA:RHEA. DR GO; GO:0019752; P:carboxylic acid metabolic process; IEA:InterPro. DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW. 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 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 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; NAD; NADP; Oxidoreductase; Reference proteome; KW Tricarboxylic acid cycle. FT CHAIN 1..308 FT /note="Malate dehydrogenase" FT /id="PRO_0000113479" FT ACT_SITE 172 FT /note="Proton acceptor" FT /evidence="ECO:0000250|UniProtKB:P61889" FT BINDING 6..11 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:Q60176" FT BINDING 79 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P61889" FT BINDING 85 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P61889" FT BINDING 92 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:Q60176" FT BINDING 115..117 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:Q60176" FT BINDING 117 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P61889" FT BINDING 148 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P61889" FT STRAND 2..5 FT /evidence="ECO:0007829|PDB:2D4A" FT HELIX 9..21 FT /evidence="ECO:0007829|PDB:2D4A" FT STRAND 26..29 FT /evidence="ECO:0007829|PDB:2D4A" FT STRAND 31..34 FT /evidence="ECO:0007829|PDB:2D4A" FT HELIX 35..50 FT /evidence="ECO:0007829|PDB:2D4A" FT STRAND 56..60 FT /evidence="ECO:0007829|PDB:2D4A" FT HELIX 62..65 FT /evidence="ECO:0007829|PDB:2D4A" FT STRAND 69..73 FT /evidence="ECO:0007829|PDB:2D4A" FT HELIX 89..106 FT /evidence="ECO:0007829|PDB:2D4A" FT STRAND 111..114 FT /evidence="ECO:0007829|PDB:2D4A" FT STRAND 116..118 FT /evidence="ECO:0007829|PDB:2D4A" FT HELIX 119..130 FT /evidence="ECO:0007829|PDB:2D4A" FT HELIX 134..136 FT /evidence="ECO:0007829|PDB:2D4A" FT STRAND 137..139 FT /evidence="ECO:0007829|PDB:2D4A" FT HELIX 142..157 FT /evidence="ECO:0007829|PDB:2D4A" FT HELIX 161..163 FT /evidence="ECO:0007829|PDB:2D4A" FT STRAND 164..170 FT /evidence="ECO:0007829|PDB:2D4A" FT STRAND 177..185 FT /evidence="ECO:0007829|PDB:2D4A" FT HELIX 190..193 FT /evidence="ECO:0007829|PDB:2D4A" FT HELIX 196..207 FT /evidence="ECO:0007829|PDB:2D4A" FT HELIX 209..217 FT /evidence="ECO:0007829|PDB:2D4A" FT HELIX 223..237 FT /evidence="ECO:0007829|PDB:2D4A" FT STRAND 242..252 FT /evidence="ECO:0007829|PDB:2D4A" FT HELIX 253..255 FT /evidence="ECO:0007829|PDB:2D4A" FT STRAND 257..268 FT /evidence="ECO:0007829|PDB:2D4A" FT STRAND 271..275 FT /evidence="ECO:0007829|PDB:2D4A" FT HELIX 282..300 FT /evidence="ECO:0007829|PDB:2D4A" FT HELIX 304..307 FT /evidence="ECO:0007829|PDB:2D4A" SQ SEQUENCE 308 AA; 33490 MW; C2A14F224650B8CE CRC64; MITILGAGKV GMATAVMLMM RGYDDLLLIA RTPGKPQGEA LDLAHAAAEL GVDIRISGSN SYEDMRGSDI VLVTAGIGRK PGMTREQLLE ANANTMADLA EKIKAYAKDA IVVITTNPVD AMTYVMYKKT GFPRERVIGF SGILDSARMA YYISQKLGVS FKSVNAIVLG MHGQKMFPVP RLSSVGGVPL EHLMSKEEIE EVVSETVNAG AKITELRGYS SNYGPAAGLV LTVEAIKRDS KRIYPYSLYL QGEYGYNDIV AEVPAVIGKS GIERIIELPL TEDEKRKFDE AVQAVKKLVE TLPPQLRE //