MDH_HALMA
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 03-AUG-2022, entry version 160.
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}.
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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 EnsemblBacteria; AAV47474; AAV47474; rrnAC2706.
DR GeneID; 40153569; -.
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 OMA; CYIIVLT; -.
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; -; 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 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; SSF51735; SSF51735; 1.
DR SUPFAM; SSF56327; SSF56327; 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
