EzCatDB: D00008

DB codeD00008
CATH domainDomain 13.40.50.720
Domain 23.90.110.10Catalytic domain
E.C.1.1.1.37
CSA1emd

CATH domainRelated DB codes (homologues)
3.40.50.720S00543,S00551,S00552,S00553,S00602,S00604,S00605,S00608,S00610,S00625,S00319,S00328,S00329,S00330,S00331,S00332,D00456,D00457,D00458,S00324,S00320,S00325,S00326,S00327,D00459,S00335,S00336,S00334,T00219,S00339,D00513,D00001,D00002,D00003,D00005,D00007,D00010,D00012,D00017,D00018,D00023,D00027,D00028,D00031,D00032,D00033,D00034,D00035,D00037,D00048,D00071,D00476,D00481,D00482,D00490,D00492,D00494,D00545,D00601,D00603,D00604,D00605,D00615,D00845,D00857,D00858,M00161,M00171,M00210,T00002,T00010,T00011,T00015,T00227,T00247,T00408,T00414,D00827,D00262,D00274,D00275,M00035,T00109
3.90.110.10D00005,M00171,D00827

Enzyme Name
Swiss-protKEGG

P61889P00346Q07841P10584P11708
Protein nameMalate dehydrogenaseMalate dehydrogenase, mitochondrialMalate dehydrogenaseMalate dehydrogenaseMalate dehydrogenase, cytoplasmicmalate dehydrogenase
malic dehydrogenase
L-malate dehydrogenase
NAD-L-malate dehydrogenase
malic acid dehydrogenase
NAD-dependent malic dehydrogenase
NAD-malate dehydrogenase
NAD-malic dehydrogenase
malate (NAD) dehydrogenase
NAD-dependent malate dehydrogenase
NAD-specific malate dehydrogenase
NAD-linked malate dehydrogenase
MDH
L-malate-NAD+ oxidoreductase
SynonymsEC 1.1.1.37
EC 1.1.1.37
EC 1.1.1.37
EC 1.1.1.37
EC 1.1.1.37
Cytosolic malate dehydrogenase

KEGG pathways
MAP codePathways
MAP00020Citrate cycle (TCA cycle)
MAP00620Pyruvate metabolism
MAP00630Glyoxylate and dicarboxylate metabolism
MAP00710Carbon fixation in photosynthetic organisms
MAP00720Reductive carboxylate cycle (CO2 fixation)

Swiss-prot:Accession NumberP61889P00346Q07841P10584P11708
Entry nameMDH_ECOLIMDHM_PIGMDH_HALMAMDH_THETHMDHC_PIG
Activity(S)-malate + NAD(+) = oxaloacetate + NADH.(S)-malate + NAD(+) = oxaloacetate + NADH.(S)-malate + NAD(+) = oxaloacetate + NADH.(S)-malate + NAD(+) = oxaloacetate + NADH.(S)-malate + NAD(+) = oxaloacetate + NADH.
SubunitHomodimer.Homodimer.Homotetramer, arranged as a dimer of dimers.Homodimer.Homodimer.
Subcellular location
Mitochondrion matrix.Cytoplasm.
Cytoplasm.
Cofactor






SubstratesProducts
KEGG-idC00149C00003C00036C00004C00080
Compound(S)-MalateNAD+OxaloacetateNADHH+
Typecarbohydrate,carboxyl groupamide group,amine group,nucleotidecarbohydrate,carboxyl groupamide group,amine group,nucleotideothers
1emdA01UnboundBound:NADUnboundUnbound
1ib6A01UnboundBound:NADUnboundUnbound
1ib6B01UnboundUnboundUnboundUnbound
1ib6C01UnboundBound:NADUnboundUnbound
1ib6D01UnboundBound:NADUnboundUnbound
1ie3A01UnboundBound:NADUnboundUnbound
1ie3B01UnboundBound:NADUnboundUnbound
1ie3C01UnboundBound:NADUnboundUnbound
1ie3D01UnboundBound:NADUnboundUnbound
2cmdA01UnboundUnboundUnboundUnbound
1mldA01UnboundUnboundUnboundUnbound
1mldB01UnboundUnboundUnboundUnbound
1mldC01UnboundUnboundUnboundUnbound
1mldD01UnboundUnboundUnboundUnbound
1d3aA02UnboundUnboundUnboundUnbound
1d3aB02UnboundUnboundUnboundUnbound
1gt2A02UnboundUnboundUnboundBound:NAD
1gt2B02UnboundUnboundUnboundBound:NAD
1hlpA02UnboundBound:NADUnboundUnbound
1hlpB02UnboundBound:NADUnboundUnbound
1o6zA02UnboundUnboundUnboundBound:NAD
1o6zB02UnboundUnboundUnboundBound:NAD
1o6zC02UnboundUnboundUnboundBound:NAD
1o6zD02UnboundUnboundUnboundBound:NAD
2hlpA02UnboundUnboundUnboundUnbound
2hlpB02UnboundUnboundUnboundUnbound
1bdmA01UnboundUnboundUnboundAnalogue:NAX
1bdmB01UnboundUnboundUnboundAnalogue:NAX
1bmdA01UnboundUnboundUnboundBound:NAD
1bmdB01UnboundUnboundUnboundBound:NAD
1iz9A01UnboundUnboundUnboundUnbound
1iz9B01UnboundUnboundUnboundUnbound
4mdhA01UnboundBound:NADUnboundUnbound
4mdhB01UnboundBound:NADUnboundUnbound
5mdhA01UnboundBound:NADUnboundUnbound
5mdhB01UnboundBound:NADUnboundUnbound
1emdA02Analogue:CITUnboundUnboundUnbound
1ib6A02UnboundUnboundUnboundUnbound
1ib6B02UnboundUnboundUnboundUnbound
1ib6C02UnboundUnboundUnboundUnbound
1ib6D02UnboundUnboundUnboundUnbound
1ie3A02UnboundUnboundUnboundUnbound
1ie3B02UnboundUnboundUnboundUnbound
1ie3C02UnboundUnboundUnboundUnbound
1ie3D02UnboundUnboundUnboundUnbound
2cmdA02Analogue:CITUnboundUnboundUnbound
1mldA02Analogue:CITUnboundUnboundUnbound
1mldB02Analogue:CITUnboundUnboundUnbound
1mldC02Analogue:CITUnboundUnboundUnbound
1mldD02Analogue:CITUnboundUnboundUnbound
1d3aA01UnboundUnboundUnboundUnbound
1d3aB01UnboundUnboundUnboundUnbound
1gt2A01UnboundUnboundUnboundUnbound
1gt2B01UnboundUnboundUnboundUnbound
1hlpA01UnboundUnboundUnboundUnbound
1hlpB01UnboundUnboundUnboundUnbound
1o6zA01UnboundUnboundUnboundUnbound
1o6zB01UnboundUnboundUnboundUnbound
1o6zC01UnboundUnboundUnboundUnbound
1o6zD01UnboundUnboundUnboundUnbound
2hlpA01UnboundUnboundUnboundUnbound
2hlpB01UnboundUnboundUnboundUnbound
1bdmA02UnboundUnboundUnboundUnbound
1bdmB02UnboundUnboundUnboundUnbound
1bmdA02UnboundUnboundUnboundUnbound
1bmdB02UnboundUnboundUnboundUnbound
1iz9A02UnboundUnboundUnboundUnbound
1iz9B02UnboundUnboundUnboundUnbound
4mdhA02UnboundUnboundUnboundUnbound
4mdhB02UnboundUnboundUnboundUnbound
5mdhA02UnboundUnboundAnalogue:MAKUnbound
5mdhB02UnboundUnboundAnalogue:MAKUnbound

Active-site residues
resource
Swiss-prot;P11708, P00346, P61889, Q07841, P10584 & literature [25]
pdbCatalytic residuescomment
1emdA01                       

1ib6A01                       

1ib6B01                       

1ib6C01                       

1ib6D01                       

1ie3A01                       

1ie3B01                       

1ie3C01                       

1ie3D01                       

2cmdA01                       

1mldA01                       

1mldB01                       

1mldC01                       

1mldD01                       

1d3aA02                       

1d3aB02                       

1gt2A02                       

1gt2B02                       

1hlpA02                       

1hlpB02                       

1o6zA02                       

1o6zB02                       

1o6zC02                       

1o6zD02                       

2hlpA02                       

2hlpB02                       

1bdmA01                       

1bdmB01                       

1bmdA01                       

1bmdB01                       

1iz9A01                       

1iz9B01                       

4mdhA01                       

4mdhB01                       

5mdhA01                       

5mdhB01                       

1emdA02ASP 150;ARG 153;HIS 177

1ib6A02ASP 150;       ;HIS 177
mutant R153C
1ib6B02ASP 150;       ;HIS 177
mutant R153C
1ib6C02ASP 150;       ;HIS 177
mutant R153C
1ib6D02ASP 150;       ;HIS 177
mutant R153C
1ie3A02ASP 150;       ;HIS 177
mutant R153C
1ie3B02ASP 150;       ;HIS 177
mutant R153C
1ie3C02ASP 150;       ;HIS 177
mutant R153C
1ie3D02ASP 150;       ;HIS 177
mutant R153C
2cmdA02ASP 150;ARG 153;HIS 177

1mldA02ASP 149;ARG 152;HIS 176

1mldB02ASP 149;ARG 152;HIS 176

1mldC02ASP 149;ARG 152;HIS 176

1mldD02ASP 149;ARG 152;HIS 176

1d3aA01ASP 168;ARG 171;HIS 195

1d3aB01ASP 168;ARG 171;HIS 195

1gt2A01ASP 168;ARG 171;HIS 195
mutant R207S, R292S
1gt2B01ASP 168;ARG 171;HIS 195
mutant R207S, R292S
1hlpA01ASP 166;ARG 169;HIS 193

1hlpB01ASP 166;ARG 169;HIS 193

1o6zA01ASP 168;ARG 171;HIS 195
mutant R207S, R292S
1o6zB01ASP 168;ARG 171;HIS 195
mutant R207S, R292S
1o6zC01ASP 168;ARG 171;HIS 195
mutant R207S, R292S
1o6zD01ASP 168;ARG 171;HIS 195
mutant R207S, R292S
2hlpA01ASP 168;ARG 171;HIS 195
mutant E267R
2hlpB01ASP 168;ARG 171;HIS 195
mutant E267R
1bdmA02ASP 158;ARG 161;HIS 186
mutant T189I
1bdmB02ASP 158;ARG 161;HIS 186
mutant T189I
1bmdA02ASP 158;ARG 161;HIS 186

1bmdB02ASP 158;ARG 161;HIS 186

1iz9A02ASP 159;ARG 162;HIS 187

1iz9B02ASP 159;ARG 162;HIS 187

4mdhA02ASP 158;ARG 161;HIS 186

4mdhB02ASP 158;ARG 161;HIS 186

5mdhA02ASP 158;ARG 161;HIS 186

5mdhB02ASP 158;ARG 161;HIS 186


References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[4]p.6077-6078
[7]p.876-877
[13]p.2084
[19]p.4811-4815
[20]

[22]

[29]Fig.3, p.261-263
[30]p.711-712

references
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Year1984
Volume226
Pages969-71
AuthorsParthasarathy R, Fridey SM
TitleConformational variability of NAD+ in the free and bound states: a nicotinamide sandwich in NAD+ crystals.
[2]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), AND PARTIAL SEQUENCE.
Medline ID87271560
PubMed ID3606987
JournalBiochemistry
Year1987
Volume26
Pages2722-34
AuthorsBirktoft JJ, Bradshaw RA, Banaszak LJ
TitleStructure of porcine heart cytoplasmic malate dehydrogenase: combining X-ray diffraction and chemical sequence data in structural studies.
Related Swiss-protP11708
[3]
PubMed ID3398050
JournalJ Mol Biol
Year1988
Volume200
Pages609-10
AuthorsHarel M, Shoham M, Frolow F, Eisenberg H, Mevarech M, Yonath A, Sussman JL
TitleCrystallization of halophilic malate dehydrogenase from Halobacterium marismortui.
[4]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID89375338
PubMed ID2775751
JournalBiochemistry
Year1989
Volume28
Pages6065-81
AuthorsBirktoft JJ, Rhodes G, Banaszak LJ
TitleRefined crystal structure of cytoplasmic malate dehydrogenase at 2.5-A resolution.
Related PDB4mdh
Related Swiss-protP11708
[5]
PubMed ID1678537
JournalPhilos Trans R Soc Lond B Biol Sci
Year1991
Volume332
Pages177-84
AuthorsDunn CR, Wilks HM, Halsall DJ, Atkinson T, Clarke AR, Muirhead H, Holbrook JJ
TitleDesign and synthesis of new enzymes based on the lactate dehydrogenase framework.
[6]
PubMed ID1445401
JournalBiochem Soc Symp
Year1992
Volume58
Pages113-25
AuthorsEisenberg H
TitleHalophilic malate dehydrogenase--a case history of biophysical investigations: ultracentrifugation, light-, X-ray- and neutron scattering.
[7]
CommentsX-RAY CRYSTALLOGRAPHY (1.87 ANGSTROMS).
Medline ID92373767
PubMed ID1507230
JournalJ Mol Biol
Year1992
Volume226
Pages867-82
AuthorsHall MD, Levitt DG, Banaszak LJ
TitleCrystal structure of Escherichia coli malate dehydrogenase. A complex of the apoenzyme and citrate at 1.87 A resolution.
Related PDB1cmd,2cmd,1cme
Related Swiss-protP61889
[8]
PubMed ID8476859
JournalBiochemistry
Year1993
Volume32
Pages4308-13
AuthorsCendrin F, Chroboczek J, Zaccai G, Eisenberg H, Mevarech M
TitleCloning, sequencing, and expression in Escherichia coli of the gene coding for malate dehydrogenase of the extremely halophilic archaebacterium Haloarcula marismortui.
[9]
CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
PubMed ID8471603
JournalBiochemistry
Year1993
Volume32
Pages3913-22
AuthorsKelly CA, Nishiyama M, Ohnishi Y, Beppu T, Birktoft JJ
TitleDeterminants of protein thermostability observed in the 1.9-A crystal structure of malate dehydrogenase from the thermophilic bacterium Thermus flavus.
Related PDB1bdm,1bmd
Related Swiss-protP10584
[10]
PubMed ID8444839
JournalJ Biol Chem
Year1993
Volume268
Pages4656-60
AuthorsNishiyama M, Birktoft JJ, Beppu T
TitleAlteration of coenzyme specificity of malate dehydrogenase from Thermus flavus by site-directed mutagenesis.
[11]
CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH NAD AND CITRATE.
PubMed ID8331658
JournalJ Mol Biol
Year1993
Volume232
Pages213-22
AuthorsHall MD, Banaszak LJ
TitleCrystal structure of a ternary complex of Escherichia coli malate dehydrogenase citrate and NAD at 1.9 A resolution.
Related PDB1emd
Related Swiss-protP61889
[12]
PubMed ID7849634
JournalBiochem Mol Biol Int
Year1994
Volume34
Pages239-50
AuthorsWani JH, Srivastava VM
TitleEffect of cations and anthelmintics on enzymes of respiratory chains of the cestode Hymenolepis diminuta.
[13]
CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
PubMed ID8117664
JournalBiochemistry
Year1994
Volume33
Pages2078-88
AuthorsGleason WB, Fu Z, Birktoft J, Banaszak L
TitleRefined crystal structure of mitochondrial malate dehydrogenase from porcine heart and the consensus structure for dicarboxylic acid oxidoreductases.
Related PDB1mld
Related Swiss-protP00346
[14]
CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID94162212
PubMed ID8011596
JournalJ Mol Graph
Year1994
Volume12
Pages14-21, 34
AuthorsDuffield ML, Nicholls DJ, Atkinson T, Scawen MD
TitleAn investigation of the thermal stabilities of two malate dehydrogenases by comparison of their three-dimensional structures.
Related Swiss-protP00346
[15]
PubMed ID7703849
JournalProtein Sci
Year1994
Volume3
Pages2023-32
AuthorsBreiter DR, Resnik E, Banaszak LJ
TitleEngineering the quaternary structure of an enzyme: construction and analysis of a monomeric form of malate dehydrogenase from Escherichia coli.
[16]
PubMed ID7601139
JournalEur J Biochem
Year1995
Volume230
Pages1088-95
AuthorsMadern D, Pfister C, Zaccai G
TitleMutation at a single acidic amino acid enhances the halophilic behaviour of malate dehydrogenase from Haloarcula marismortui in physiological salts.
[17]
PubMed ID7476321
JournalMetabolism
Year1995
Volume44
Pages1380-3
AuthorsPetersen KF, Blair JB, Shulman GI
TitleTriiodothyronine treatment increases substrate cycling between pyruvate carboxylase and malic enzyme in perfused rat liver.
[18]
PubMed ID8901548
JournalProc Natl Acad Sci U S A
Year1996
Volume93
Pages12150-4
AuthorsPlochocka D, Welnicki M, Zielenkiewicz P, Ostoja-Zagorski W
TitleThree-dimensional model of the potyviral genome-linked protein.
[19]
PubMed ID9125501
JournalBiochemistry
Year1997
Volume36
Pages4800-16
AuthorsCunningham MA, Ho LL, Nguyen DT, Gillilan RE, Bash PA
TitleSimulation of the enzyme reaction mechanism of malate dehydrogenase.
[20]
PubMed ID9692968
JournalBiochemistry
Year1998
Volume37
Pages10780-91
AuthorsJairajpuri MA, Azam N, Baburaj K, Bulliraju E, Durani S
TitleCharge and solvation effects in anion recognition centers: an inquiry exploiting reactive arginines.
[21]
CommentsX-ray crystallography
PubMed ID10206992
JournalJ Biol Chem
Year1999
Volume274
Pages11761-7
AuthorsKim SY, Hwang KY, Kim SH, Sung HC, Han YS, Cho Y
TitleStructural basis for cold adaptation. Sequence, biochemical properties, and crystal structure of malate dehydrogenase from a psychrophile Aquaspirillium arcticum.
Related PDB1b8p
[22]
CommentsX-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
Medline ID99173114
PubMed ID10075524
JournalJ Mol Biol
Year1999
Volume285
Pages703-12
AuthorsChapman AD, Cortes A, Dafforn TR, Clarke AR, Brady RL
TitleStructural basis of substrate specificity in malate dehydrogenases: crystal structure of a ternary complex of porcine cytoplasmic malate dehydrogenase, alpha-ketomalonate and tetrahydoNAD.
Related PDB5mdh
Related Swiss-protP11708
[23]
PubMed ID10653644
JournalBiochemistry
Year2000
Volume39
Pages1001-10
AuthorsMadern D, Ebel C, Mevarech M, Richard SB, Pfister C, Zaccai G
TitleInsights into the molecular relationships between malate and lactate dehydrogenases: structural and biochemical properties of monomeric and dimeric intermediates of a mutant of tetrameric L-[LDH-like] malate dehydrogenase from the halophilic archaeon Haloarcula marismortui.
[24]
CommentsX-ray crystallography
PubMed ID10653643
JournalBiochemistry
Year2000
Volume39
Pages992-1000
AuthorsRichard SB, Madern D, Garcin E, Zaccai G
TitleHalophilic adaptation: novel solvent protein interactions observed in the 2.9 and 2.6 A resolution structures of the wild type and a mutant of malate dehydrogenase from Haloarcula marismortui.
Related PDB1d3a,2hlp
[25]
CommentsX-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH NAD AND PYRUVATE, AND MUTAGENESIS OF ARG-153.
PubMed ID11389141
JournalJ Biol Chem
Year2001
Volume276
Pages31156-62
AuthorsBell JK, Yennawar HP, Wright SK, Thompson JR, Viola RE, Banaszak LJ
TitleStructural analyses of a malate dehydrogenase with a variable active site.
Related PDB1ib6,1ie3
Related Swiss-protP61889
[26]
PubMed ID11292347
JournalJ Mol Biol
Year2001
Volume307
Pages1351-62
AuthorsLee BI, Chang C, Cho SJ, Eom SH, Kim KK, Yu YG, Suh SW
TitleCrystal structure of the MJ0490 gene product of the hyperthermophilic archaebacterium Methanococcus jannaschii, a novel member of the lactate/malate family of dehydrogenases.
[27]
PubMed ID11473265
JournalNat Struct Biol
Year2001
Volume8
Pages721-8
AuthorsChen J, Walter S, Horwich AL, Smith DL
TitleFolding of malate dehydrogenase inside the GroEL-GroES cavity.
[28]
PubMed ID11742111
JournalProtein Eng
Year2001
Volume14
Pages911-7
AuthorsTrejo F, Gelpi JL, Ferrer A, Boronat A, Busquets M, Cortes A
TitleContribution of engineered electrostatic interactions to the stability of cytosolic malate dehydrogenase.
[29]
PubMed ID12537350
JournalGen Physiol Biophys
Year2002
Volume21
Pages257-65
AuthorsMinarik P, Tomaskova N, Kollarova M, Antalik M
TitleMalate dehydrogenases--structure and function.
[30]
PubMed ID12054817
JournalJ Mol Biol
Year2002
Volume318
Pages707-21
AuthorsDalhus B, Saarinen M, Sauer UH, Eklund P, Johansson K, Karlsson A, Ramaswamy S, Bjork A, Synstad B, Naterstad K, Sirevag R, Eklund H
TitleStructural basis for thermophilic protein stability: structures of thermophilic and mesophilic malate dehydrogenases.
[31]
PubMed ID14572663
JournalFEBS Lett
Year2003
Volume553
Pages423-6
AuthorsBjork A, Mantzilas D, Sirevag R, Eijsink VG
TitleElectrostatic interactions across the dimer-dimer interface contribute to the pH-dependent stability of a tetrameric malate dehydrogenase.
[32]
CommentsX-ray crystallography
PubMed ID12581646
JournalJ Mol Biol
Year2003
Volume326
Pages859-73
AuthorsIrimia A, Ebel C, Madern D, Richard SB, Cosenza LW, Zaccai G, Vellieux FM
TitleThe Oligomeric states of Haloarcula marismortui malate dehydrogenase are modulated by solvent components as shown by crystallographic and biochemical studies.
Related PDB1gt2,1o6z
[33]
PubMed ID14659762
JournalJ Mol Biol
Year2004
Volume335
Pages343-56
AuthorsIrimia A, Vellieux FM, Madern D, Zaccai G, Karshikoff A, Tibbelin G, Ladenstein R, Lien T, Birkeland NK
TitleThe 2.9A resolution crystal structure of malate dehydrogenase from Archaeoglobus fulgidus: mechanisms of oligomerisation and thermal stabilisation.

comments
This enzyme catalyzes the following reaction:
(A) Hydride transfer from substrate, (S)-malate, to NAD(+):

createdupdated
2004-03-242009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

© Computational Biology Research Center, AIST, 2004 All Rights Reserved.