ID MDH_HALMA Reviewed; 304 AA. AC Q07841; Q5UZ29; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1994, sequence version 1. DT 27-MAR-2024, entry version 166. DE RecName: Full=Malate dehydrogenase {ECO:0000303|PubMed:8476859}; DE EC=1.1.1.37 {ECO:0000269|PubMed:8476859}; GN Name=mdh; OrderedLocusNames=rrnAC2706; OS Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM OS B-1809) (Halobacterium marismortui). OC Archaea; Euryarchaeota; Stenosarchaea group; Halobacteria; Halobacteriales; OC Haloarculaceae; Haloarcula. OX NCBI_TaxID=272569; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-55, FUNCTION, RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, RP AND MUTAGENESIS OF ARG-83. RX PubMed=8476859; DOI=10.1021/bi00067a020; RA Cendrin F., Chroboczek J., Zaccai G., Eisenberg H., Mevarech M.; RT "Cloning, sequencing, and expression in Escherichia coli of the gene coding RT for malate dehydrogenase of the extremely halophilic archaebacterium RT Haloarcula marismortui."; RL Biochemistry 32:4308-4313(1993). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809; RX PubMed=15520287; DOI=10.1101/gr.2700304; RA Baliga N.S., Bonneau R., Facciotti M.T., Pan M., Glusman G., Deutsch E.W., RA Shannon P., Chiu Y., Weng R.S., Gan R.R., Hung P., Date S.V., Marcotte E., RA Hood L., Ng W.V.; RT "Genome sequence of Haloarcula marismortui: a halophilic archaeon from the RT Dead Sea."; RL Genome Res. 14:2221-2234(2004). RN [3] RP SUBUNIT. RX PubMed=10653644; DOI=10.1021/bi9910023; RA Madern D., Ebel C., Mevarech M., Richard S.B., Pfister C., Zaccai G.; RT "Insights into the molecular relationships between malate and lactate RT dehydrogenases: structural and biochemical properties of monomeric and RT dimeric intermediates of a mutant of tetrameric L-[LDH-like] malate RT dehydrogenase from the halophilic archaeon Haloarcula marismortui."; RL Biochemistry 39:1001-1010(2000). RN [4] RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS). RA Dym O., Mevarech M., Sussman J.L.; RT "Structural features that stabilize halophilic malate-dehydrogenase from an RT archaebacterium."; RL Science 267:1344-1346(1995). RN [5] RP X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS), AND SUBUNIT. RX PubMed=10653643; DOI=10.1021/bi991001a; RA Richard S.B., Madern D., Garcin E., Zaccai G.; RT "Halophilic adaptation: novel solvent protein interactions observed in the RT 2.9 and 2.6 A resolution structures of the wild type and a mutant of malate RT dehydrogenase from Haloarcula marismortui."; RL Biochemistry 39:992-1000(2000). RN [6] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH NAD, AND SUBUNIT. RX PubMed=12581646; DOI=10.1016/s0022-2836(02)01450-x; RA Irimia A., Ebel C., Madern D., Richard S.B., Cosenza L.W., Zaccai G., RA Vellieux F.M.D.; RT "The oligomeric states of Haloarcula marismortui malate dehydrogenase are RT modulated by solvent components as shown by crystallographic and RT biochemical studies."; RL J. Mol. Biol. 326:859-873(2003). CC -!- FUNCTION: Catalyzes the reversible oxidation of malate to oxaloacetate. CC {ECO:0000269|PubMed:8476859}. 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:0000269|PubMed:8476859}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.9 mM for oxaloacetate (in the presence of 2 M NaCl) CC {ECO:0000269|PubMed:8476859}; CC KM=0.7 mM for oxaloacetate (in the presence of 4 M NaCl) CC {ECO:0000269|PubMed:8476859}; CC Note=kcat is 197 sec(-1) with oxaloacetate as substrate (in the CC presence of 2 M NaCl). kcat is 69 sec(-1) with oxaloacetate as CC substrate (in the presence of 4 M NaCl).; CC -!- SUBUNIT: Homotetramer; arranged as a dimer of dimers. CC {ECO:0000269|PubMed:10653643, ECO:0000269|PubMed:10653644, CC ECO:0000269|PubMed:12581646}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:8476859}. CC -!- MISCELLANEOUS: The quaternary structure is stabilized by chloride ions CC bound between the subunits. This may be an adaptation to the halophilic CC environment. 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; M97218; AAA73368.1; -; Genomic_DNA. DR EMBL; AY596297; AAV47474.1; -; Genomic_DNA. DR PIR; A49496; A49496. DR RefSeq; WP_004959949.1; NZ_CP039138.1. DR PDB; 1D3A; X-ray; 2.94 A; A/B=2-304. DR PDB; 1HLP; X-ray; 3.20 A; A/B=2-304. DR PDB; 1O6Z; X-ray; 1.95 A; A/B/C/D=2-304. DR PDB; 2HLP; X-ray; 2.59 A; A/B=2-304. DR PDB; 2J5K; X-ray; 2.00 A; A/B/C/D=1-304. DR PDB; 2J5Q; X-ray; 2.15 A; A/B/C/D=1-304. DR PDB; 2J5R; X-ray; 2.25 A; A/B/C/D=1-304. DR PDB; 2X0R; X-ray; 2.92 A; A/B=1-304. DR PDB; 4JCO; X-ray; 1.70 A; A/B/C/D=1-304. DR PDB; 7Q3X; X-ray; 1.95 A; A/B/C/D=2-304. DR PDBsum; 1D3A; -. DR PDBsum; 1HLP; -. DR PDBsum; 1O6Z; -. DR PDBsum; 2HLP; -. DR PDBsum; 2J5K; -. DR PDBsum; 2J5Q; -. DR PDBsum; 2J5R; -. DR PDBsum; 2X0R; -. DR PDBsum; 4JCO; -. DR PDBsum; 7Q3X; -. DR AlphaFoldDB; Q07841; -. DR SMR; Q07841; -. DR STRING; 272569.rrnAC2706; -. DR PaxDb; 272569-rrnAC2706; -. DR EnsemblBacteria; AAV47474; AAV47474; rrnAC2706. DR GeneID; 64824029; -. DR KEGG; hma:rrnAC2706; -. DR PATRIC; fig|272569.17.peg.3289; -. DR eggNOG; arCOG00246; Archaea. DR HOGENOM; CLU_045401_1_1_2; -. DR BRENDA; 1.1.1.37; 2549. DR EvolutionaryTrace; Q07841; -. DR Proteomes; UP000001169; Chromosome I. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0030060; F:L-malate dehydrogenase activity; IEA:UniProtKB-EC. 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 NCBIfam; NF041314; Malate_DH_Halo; 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; Cytoplasm; Direct protein sequencing; NAD; Oxidoreductase; KW Reference proteome; Tricarboxylic acid cycle. FT CHAIN 1..304 FT /note="Malate dehydrogenase" FT /id="PRO_0000113481" FT ACT_SITE 176 FT /note="Proton acceptor" FT /evidence="ECO:0000250|UniProtKB:P61889" FT BINDING 8..14 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:12581646" FT BINDING 34 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:12581646" FT BINDING 83 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P61889" FT BINDING 89 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P61889" FT BINDING 96 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:12581646" FT BINDING 119..121 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:12581646" FT BINDING 121 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P61889" FT BINDING 152 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P61889" FT MUTAGEN 83 FT /note="R->Q: Substrate specificity changes from FT oxaloacetate to pyruvate." FT /evidence="ECO:0000269|PubMed:8476859" FT CONFLICT 19 FT /note="Y -> T (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT STRAND 3..7 FT /evidence="ECO:0007829|PDB:4JCO" FT TURN 8..10 FT /evidence="ECO:0007829|PDB:4JCO" FT HELIX 12..23 FT /evidence="ECO:0007829|PDB:4JCO" FT STRAND 28..33 FT /evidence="ECO:0007829|PDB:4JCO" FT HELIX 36..38 FT /evidence="ECO:0007829|PDB:4JCO" FT HELIX 39..53 FT /evidence="ECO:0007829|PDB:4JCO" FT TURN 54..56 FT /evidence="ECO:0007829|PDB:4JCO" FT STRAND 60..63 FT /evidence="ECO:0007829|PDB:4JCO" FT HELIX 66..69 FT /evidence="ECO:0007829|PDB:4JCO" FT STRAND 73..77 FT /evidence="ECO:0007829|PDB:4JCO" FT HELIX 89..108 FT /evidence="ECO:0007829|PDB:4JCO" FT STRAND 115..118 FT /evidence="ECO:0007829|PDB:4JCO" FT HELIX 123..133 FT /evidence="ECO:0007829|PDB:4JCO" FT STRAND 134..136 FT /evidence="ECO:0007829|PDB:1O6Z" FT HELIX 138..140 FT /evidence="ECO:0007829|PDB:4JCO" FT STRAND 141..143 FT /evidence="ECO:0007829|PDB:4JCO" FT HELIX 146..161 FT /evidence="ECO:0007829|PDB:4JCO" FT HELIX 165..167 FT /evidence="ECO:0007829|PDB:4JCO" FT STRAND 172..174 FT /evidence="ECO:0007829|PDB:4JCO" FT STRAND 180..182 FT /evidence="ECO:0007829|PDB:4JCO" FT HELIX 184..186 FT /evidence="ECO:0007829|PDB:4JCO" FT HELIX 198..216 FT /evidence="ECO:0007829|PDB:4JCO" FT TURN 217..219 FT /evidence="ECO:0007829|PDB:4JCO" FT HELIX 224..238 FT /evidence="ECO:0007829|PDB:4JCO" FT STRAND 244..253 FT /evidence="ECO:0007829|PDB:4JCO" FT HELIX 254..256 FT /evidence="ECO:0007829|PDB:4JCO" FT STRAND 258..269 FT /evidence="ECO:0007829|PDB:4JCO" FT STRAND 272..276 FT /evidence="ECO:0007829|PDB:4JCO" FT HELIX 283..303 FT /evidence="ECO:0007829|PDB:4JCO" SQ SEQUENCE 304 AA; 32808 MW; 0B5B630158CAD083 CRC64; MTKVSVVGAA GTVGAAAGYN IALRDIADEV VFVDIPDKED DTVGQAADTN HGIAYDSNTR VRQGGYEDTA GSDVVVITAG IPRQPGQTRI DLAGDNAPIM EDIQSSLDEH NDDYISLTTS NPVDLLNRHL YEAGDRSREQ VIGFGGRLDS ARFRYVLSEE FDAPVQNVEG TILGEHGDAQ VPVFSKVRVD GTDPEFSGDE KEQLLGDLQE SAMDVIERKG ATEWGPARGV AHMVEAILHD TGEVLPASVK LEGEFGHEDT AFGVPVRLGS NGVEEIVEWD LDDYEQDLMA DAAEKLSDQY DKIS //