EzCatDB: M00171
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DB codeM00171
CATH domainDomain 13.40.50.720 : Rossmann fold
Domain 23.90.110.10 : L-2-Hydroxyisocaproate Dehydrogenase; Chain A, domain 2Catalytic domain
Domain 34.-.-.-Catalytic domain
Domain 44.-.-.-Catalytic domain
E.C.1.1.1.82

CATH domainRelated DB codes (homologues)
3.40.50.720 : Rossmann foldS00543,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,D00008,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,M00210,T00002,T00010,T00011,T00015,T00227,T00247,T00408,T00414,D00827,D00262,D00274,D00275,M00035,T00109
3.90.110.10 : L-2-Hydroxyisocaproate Dehydrogenase; Chain A, domain 2D00005,D00008,D00827

Enzyme Name
UniProtKBKEGG

P46489P17606
Protein nameMalate dehydrogenase [NADP], chloroplasticMalate dehydrogenase [NADP] 1, chloroplasticmalate dehydrogenase (NADP+)
NADP+-malic enzyme
NADP+-malate dehydrogenase
malic dehydrogenase (nicotinamide adenine dinucleotide phosphate)
malate NADP+ dehydrogenase
NADP+ malate dehydrogenase
NADP+-linked malate dehydrogenase
malate dehydrogenase (NADP+)
SynonymsEC 1.1.1.82
NADP-MDH
EC 1.1.1.82
NADP-MDH-1
RefSeq
XP_002445670.1 (Protein)
XM_002445625.1 (DNA/RNA sequence)
PfamPF02866 (Ldh_1_C)
PF00056 (Ldh_1_N)
[Graphical view]
PF02866 (Ldh_1_C)
PF00056 (Ldh_1_N)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00620Pyruvate metabolism
MAP00710Carbon fixation in photosynthetic organisms

UniProtKB:Accession NumberP46489P17606
Entry nameMDHP_FLABIMDHP1_SORBI
Activity(S)-malate + NADP(+) = oxaloacetate + NADPH.(S)-malate + NADP(+) = oxaloacetate + NADPH.
SubunitHomodimer.Homodimer.
Subcellular locationPlastid, chloroplast.Plastid, chloroplast.
Cofactor


Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00149C00006C00036C00005C00080
Compound(S)-MalateNADP+OxaloacetateNADPHH+
Typecarbohydrate,carboxyl groupamide group,amine group,nucleotidecarbohydrate,carboxyl groupamide group,amine group,nucleotideothers
ChEBI30797
18009
30744
16474
15378
PubChem222656
5886
970
5884
1038
             
1civA01UnboundBound:NAPUnboundUnbound 
7mdhA01UnboundUnboundUnboundUnbound 
7mdhB01UnboundUnboundUnboundUnbound 
7mdhC01UnboundUnboundUnboundUnbound 
7mdhD01UnboundUnboundUnboundUnbound 
1civA02UnboundUnboundUnboundUnbound 
7mdhA02UnboundUnboundUnboundUnbound 
7mdhB02UnboundUnboundUnboundUnbound 
7mdhC02UnboundUnboundUnboundUnbound 
7mdhD02UnboundUnboundUnboundUnbound 
1civA03UnboundUnboundUnboundUnbound 
7mdhA03UnboundUnboundUnboundUnbound 
7mdhB03UnboundUnboundUnboundUnbound 
7mdhC03UnboundUnboundUnboundUnbound 
7mdhD03UnboundUnboundUnboundUnbound 
1civA04UnboundUnboundUnboundUnbound 
7mdhA04UnboundUnboundUnboundUnbound 
7mdhB04UnboundUnboundUnboundUnbound 
7mdhC04UnboundUnboundUnboundUnbound 
7mdhD04UnboundUnboundUnboundUnbound 

Active-site residues
resource
PDB;7mdh & Swiss-prot;P46489, P17606 & literature [9], [10]
pdbCatalytic residues
         
1civA01 
7mdhA01 
7mdhB01 
7mdhC01 
7mdhD01 
1civA02ASP 197;HIS 225;CYS 361
7mdhA02ASP 201;HIS 229;CYS 365
7mdhB02ASP 201;HIS 229;CYS 365
7mdhC02ASP 201;HIS 229;CYS 365
7mdhD02ASP 201;HIS 229;CYS 365
1civA03CYS  20;CYS  25
7mdhA03CYS  24;CYS  29
7mdhB03CYS  24;CYS  29
7mdhC03CYS  24;CYS  29
7mdhD03CYS  24;CYS  29
1civA04CYS 373
7mdhA04CYS 377
7mdhB04CYS 377
7mdhC04CYS 377
7mdhD04CYS 377

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[4]Fig.1, p.72-73
[8]Fig.8, p.3516-3517
[10]

[11]

[14]p.193
[15]p.33486-33487
[16]p.4325
[18]

[19]


references
[1]
PubMed ID3586023
JournalJ Mol Biol
Year1987
Volume193
Pages233-5
AuthorsBaker PJ, Thomas DH, Barton CH, Rice DW, Bailey E
TitleCrystallization of an NADP+-dependent malic enzyme from rat liver.
[2]
PubMed ID3341764
JournalArch Biochem Biophys
Year1988
Volume260
Pages771-9
AuthorsFickenscher K, Scheibe R
TitleLimited proteolysis of inactive tetrameric chloroplast NADP-malate dehydrogenase produces active dimers.
[3]
PubMed ID2351138
JournalEur J Biochem
Year1990
Volume189
Pages581-7
AuthorsScheibe R, Rudolph R, Reng W, Jaenicke R
TitleStructural and catalytic properties of oxidized and reduced chloroplast NADP-malate dehydrogenase upon denaturation and renaturation.
[4]
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.
[5]
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.
[6]
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.
[7]
PubMed ID7918997
JournalBiophys J
Year1994
Volume67
Pages29-35
AuthorsLi D, Stevens FJ, Schiffer M, Anderson LE
TitleMechanism of light modulation: identification of potential redox-sensitive cysteines distal to catalytic site in light-activated chloroplast enzymes.
[8]
PubMed ID8106392
JournalJ Biol Chem
Year1994
Volume269
Pages3511-7
AuthorsIssakidis E, Saarinen M, Decottignies P, Jacquot JP, Cretin C, Gadal P, Miginiac-Maslow M
TitleIdentification and characterization of the second regulatory disulfide bridge of recombinant sorghum leaf NADP-malate dehydrogenase.
[9]
PubMed ID7961639
JournalJ Biol Chem
Year1994
Volume269
Pages27291-6
AuthorsLemaire M, Schmitter JM, Issakidis E, Miginiac-Maslow M, Gadal P, Decottignies P
TitleEssential histidine at the active site of sorghum leaf NADP-dependent malate dehydrogenase.
[10]
PubMed ID8665917
JournalEur J Biochem
Year1996
Volume236
Pages947-52
AuthorsLemaire M, Miginiac-Maslow M, Decottignies P
TitleThe catalytic site of chloroplastic NADP-dependent malate dehydrogenase contains a His/Asp pair.
[11]
PubMed ID8772188
JournalFEBS Lett
Year1996
Volume392
Pages121-4
AuthorsIssakidis E, Lemaire M, Decottignies P, Jacquot JP, Miginiac-Maslow M
TitleDirect evidence for the different roles of the N- and C-terminal regulatory disulfides of sorghum leaf NADP-malate dehydrogenase in its activation by reduced thioredoxin.
[12]
PubMed ID8612735
JournalFEBS Lett
Year1996
Volume382
Pages137-40
AuthorsLemaire M, Issakidis E, Ruelland E, Decottignies P, Miginiac-Maslow M
TitleAn active-site cysteine of sorghum leaf NADP-malate dehydrogenase studied by site-directed mutagenesis.
[13]
CommentsCRYSTALLIZATION.
PubMed ID9761865
JournalActa Crystallogr D Biol Crystallogr
Year1998
Volume54
Pages654-6
AuthorsMacPherson KH, Ashton AR, Carr PD, Trevanion SJ, Verger D, Ollis DL
TitleCrystallization and preliminary crystallographic studies of chloroplast NADP-dependent malate dehydrogenase from Flaveria bidentis.
Related UniProtKBP46489
[14]
PubMed ID9692918
JournalEur J Biochem
Year1998
Volume255
Pages185-95
AuthorsKrimm I, Lemaire S, Ruelland E, Miginiac-Maslow M, Jaquot JP, Hirasawa M, Knaff DB, Lancelin JM
TitleThe single mutation Trp35-->Ala in the 35-40 redox site of Chlamydomonas reinhardtii thioredoxin h affects its biochemical activity and the pH dependence of C36-C39 1H-13C NMR.
[15]
PubMed ID9837927
JournalJ Biol Chem
Year1998
Volume273
Pages33482-8
AuthorsRuelland E, Johansson K, Decottignies P, Djukic N, Miginiac-Maslow M
TitleThe autoinhibition of sorghum NADP malate dehydrogenase is mediated by a C-terminal negative charge.
[16]
CommentsX-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
PubMed ID10194350
JournalBiochemistry
Year1999
Volume38
Pages4319-26
AuthorsJohansson K, Ramaswamy S, Saarinen M, Lemaire-Chamley M, Issakidis-Bourguet E, Miginiac-Maslow M, Eklund H
TitleStructural basis for light activation of a chloroplast enzyme: the structure of sorghum NADP-malate dehydrogenase in its oxidized form.
Related PDB7mdh
Related UniProtKBP17606
[17]
PubMed ID10574915
JournalJ Biol Chem
Year1999
Volume274
Pages34539-42
AuthorsKrimm I, Goyer A, Issakidis-Bourguet E, Miginiac-Maslow M, Lancelin JM
TitleDirect NMR observation of the thioredoxin-mediated reduction of the chloroplast NADP-malate dehydrogenase provides a structural basis for the relief of autoinhibition.
[18]
CommentsX-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
PubMed ID10196131
JournalStructure Fold Des
Year1999
Volume7
Pages461-75
AuthorsCarr PD, Verger D, Ashton AR, Ollis DL
TitleChloroplast NADP-malate dehydrogenase: structural basis of light-dependent regulation of activity by thiol oxidation and reduction.
Related PDB1civ
Related UniProtKBP46489
[19]
PubMed ID10913357
JournalBiochem Biophys Res Commun
Year2000
Volume274
Pages440-4
AuthorsYang Z, Batra R, Floyd DL, Hung HC, Chang GG, Tong L
TitlePotent and competitive inhibition of malic enzymes by lanthanide ions.
[20]
PubMed ID10767431
JournalFEBS Lett
Year2000
Volume471
Pages240-4
AuthorsSchepens I, Decottignies P, Ruelland E, Johansson K, Miginiac-Maslow M
TitleThe dimer contact area of sorghum NADP-malate dehydrogenase: role of aspartate 101 in dimer stability and catalytic activity.
[21]
PubMed ID10801830
JournalJ Biol Chem
Year2000
Volume275
Pages20996-1001
AuthorsSchepens I, Johansson K, Decottignies P, Gillibert M, Hirasawa M, Knaff DB, Miginiac-Maslow M
TitleInhibition of the thioredoxin-dependent activation of the NADP-malate dehydrogenase and cofactor specificity.
[22]
PubMed ID10958800
JournalJ Biol Chem
Year2000
Volume275
Pages35792-8
AuthorsSchepens I, Ruelland E, Miginiac-Maslow M, Le Marechal P, Decottignies P
TitleThe role of active site arginines of sorghum NADP-malate dehydrogenase in thioredoxin-dependent activation and activity.
[23]
PubMed ID11025545
JournalProteins
Year2000
Volume41
Pages334-49
AuthorsLancelin JM, Guilhaudis L, Krimm I, Blackledge MJ, Marion D, Jacquot JP
TitleNMR structures of thioredoxin m from the green alga Chlamydomonas reinhardtii.
[24]
PubMed ID11172800
JournalFEBS Lett
Year2001
Volume490
Pages1-6
AuthorsDrincovich MF, Casati P, Andreo CS
TitleNADP-malic enzyme from plants: a ubiquitous enzyme involved in different metabolic pathways.
[25]
PubMed ID11576537
JournalFEBS Lett
Year2001
Volume505
Pages405-8
AuthorsGoyer A, Decottignies P, Issakidis-Bourguet E, Miginiac-Maslow M
TitleSites of interaction of thioredoxin with sorghum NADP-malate dehydrogenase.
[26]
PubMed ID12562758
JournalJ Biol Chem
Year2003
Volume278
Pages13757-64
AuthorsDetarsio E, Wheeler MC, Campos Bermudez VA, Andreo CS, Drincovich MF
TitleMaize C4 NADP-malic enzyme. Expression in Escherichia coli and characterization of site-directed mutants at the putative nucleoside-binding sites.

comments
Although this enzyme is assigned only two domains in the CATH classification, the N-terminal and C-terminal regions are assigned as the third and fourth domains, as the N-terminal region is important in terms of catalysis.
There seem to be three distinct active sites, two of which are disulfide-bonds of two cysteine residues at the N-terminal and C-terminal regions.

createdupdated
2004-03-162009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
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Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
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)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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