DB code: M00171

CATH domain 3.40.50.720 : Rossmann fold
3.90.110.10 : L-2-Hydroxyisocaproate Dehydrogenase; Chain A, domain 2 Catalytic domain
4.-.-.- : Catalytic domain
4.-.-.- : Catalytic domain
E.C. 1.1.1.82
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.90.110.10 : L-2-Hydroxyisocaproate Dehydrogenase; Chain A, domain 2 D00005 D00008 D00827
3.40.50.720 : Rossmann fold S00543 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam RefSeq
P46489 Malate dehydrogenase [NADP], chloroplastic
EC 1.1.1.82
NADP-MDH
PF02866 (Ldh_1_C)
PF00056 (Ldh_1_N)
[Graphical View]
P17606 Malate dehydrogenase [NADP] 1, chloroplastic
EC 1.1.1.82
NADP-MDH-1
PF02866 (Ldh_1_C)
PF00056 (Ldh_1_N)
[Graphical View]
XP_002445670.1 (Protein)
XM_002445625.1 (DNA/RNA sequence)

KEGG enzyme name
malate 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+)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P17606 MDHP1_SORBI (S)-malate + NADP(+) = oxaloacetate + NADPH. Homodimer. Plastid, chloroplast.
P46489 MDHP_FLABI (S)-malate + NADP(+) = oxaloacetate + NADPH. Homodimer. Plastid, chloroplast.

KEGG Pathways
Map code Pathways E.C.
MAP00710 Carbon fixation in photosynthetic organisms
MAP00620 Pyruvate metabolism

Compound table
Substrates Products Intermediates
KEGG-id C00149 C00006 C00036 C00005 C00080
E.C.
Compound (S)-Malate NADP+ Oxaloacetate NADPH H+
Type carbohydrate,carboxyl group amide group,amine group,nucleotide carbohydrate,carboxyl group amide group,amine group,nucleotide others
ChEBI 30797
18009
30744
16474
15378
PubChem 222656
5886
970
5884
1038
1civA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:NAP Unbound Unbound
7mdhA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
7mdhB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
7mdhC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
7mdhD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1civA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
7mdhA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
7mdhB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
7mdhC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
7mdhD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1civA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
7mdhA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
7mdhB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
7mdhC03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
7mdhD03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1civA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
7mdhA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
7mdhB04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
7mdhC04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
7mdhD04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
PDB;7mdh & Swiss-prot;P46489, P17606 & literature [9], [10]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1civA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
7mdhA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
7mdhB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
7mdhC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
7mdhD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1civA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 197;HIS 225;CYS 361
7mdhA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 201;HIS 229;CYS 365
7mdhB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 201;HIS 229;CYS 365
7mdhC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 201;HIS 229;CYS 365
7mdhD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 201;HIS 229;CYS 365
1civA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 20;CYS 25
7mdhA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 24;CYS 29
7mdhB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 24;CYS 29
7mdhC03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 24;CYS 29
7mdhD03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 24;CYS 29
1civA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 373
7mdhA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 377
7mdhB04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 377
7mdhC04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 377
7mdhD04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 377

References for Catalytic Mechanism
References Sections No. 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]
Resource
Comments
Medline ID
PubMed ID 3586023
Journal J Mol Biol
Year 1987
Volume 193
Pages 233-5
Authors Baker PJ, Thomas DH, Barton CH, Rice DW, Bailey E
Title Crystallization of an NADP+-dependent malic enzyme from rat liver.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 3341764
Journal Arch Biochem Biophys
Year 1988
Volume 260
Pages 771-9
Authors Fickenscher K, Scheibe R
Title Limited proteolysis of inactive tetrameric chloroplast NADP-malate dehydrogenase produces active dimers.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 2351138
Journal Eur J Biochem
Year 1990
Volume 189
Pages 581-7
Authors Scheibe R, Rudolph R, Reng W, Jaenicke R
Title Structural and catalytic properties of oxidized and reduced chloroplast NADP-malate dehydrogenase upon denaturation and renaturation.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 1678537
Journal Philos Trans R Soc Lond B Biol Sci
Year 1991
Volume 332
Pages 177-84
Authors Dunn CR, Wilks HM, Halsall DJ, Atkinson T, Clarke AR, Muirhead H, Holbrook JJ
Title Design and synthesis of new enzymes based on the lactate dehydrogenase framework.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 8444839
Journal J Biol Chem
Year 1993
Volume 268
Pages 4656-60
Authors Nishiyama M, Birktoft JJ, Beppu T
Title Alteration of coenzyme specificity of malate dehydrogenase from Thermus flavus by site-directed mutagenesis.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 8331658
Journal J Mol Biol
Year 1993
Volume 232
Pages 213-22
Authors Hall MD, Banaszak LJ
Title Crystal structure of a ternary complex of Escherichia coli malate dehydrogenase citrate and NAD at 1.9 A resolution.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 7918997
Journal Biophys J
Year 1994
Volume 67
Pages 29-35
Authors Li D, Stevens FJ, Schiffer M, Anderson LE
Title Mechanism of light modulation: identification of potential redox-sensitive cysteines distal to catalytic site in light-activated chloroplast enzymes.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 8106392
Journal J Biol Chem
Year 1994
Volume 269
Pages 3511-7
Authors Issakidis E, Saarinen M, Decottignies P, Jacquot JP, Cretin C, Gadal P, Miginiac-Maslow M
Title Identification and characterization of the second regulatory disulfide bridge of recombinant sorghum leaf NADP-malate dehydrogenase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 7961639
Journal J Biol Chem
Year 1994
Volume 269
Pages 27291-6
Authors Lemaire M, Schmitter JM, Issakidis E, Miginiac-Maslow M, Gadal P, Decottignies P
Title Essential histidine at the active site of sorghum leaf NADP-dependent malate dehydrogenase.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 8665917
Journal Eur J Biochem
Year 1996
Volume 236
Pages 947-52
Authors Lemaire M, Miginiac-Maslow M, Decottignies P
Title The catalytic site of chloroplastic NADP-dependent malate dehydrogenase contains a His/Asp pair.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 8772188
Journal FEBS Lett
Year 1996
Volume 392
Pages 121-4
Authors Issakidis E, Lemaire M, Decottignies P, Jacquot JP, Miginiac-Maslow M
Title Direct 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.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 8612735
Journal FEBS Lett
Year 1996
Volume 382
Pages 137-40
Authors Lemaire M, Issakidis E, Ruelland E, Decottignies P, Miginiac-Maslow M
Title An active-site cysteine of sorghum leaf NADP-malate dehydrogenase studied by site-directed mutagenesis.
Related PDB
Related UniProtKB
[13]
Resource
Comments CRYSTALLIZATION.
Medline ID
PubMed ID 9761865
Journal Acta Crystallogr D Biol Crystallogr
Year 1998
Volume 54
Pages 654-6
Authors MacPherson KH, Ashton AR, Carr PD, Trevanion SJ, Verger D, Ollis DL
Title Crystallization and preliminary crystallographic studies of chloroplast NADP-dependent malate dehydrogenase from Flaveria bidentis.
Related PDB
Related UniProtKB P46489
[14]
Resource
Comments
Medline ID
PubMed ID 9692918
Journal Eur J Biochem
Year 1998
Volume 255
Pages 185-95
Authors Krimm I, Lemaire S, Ruelland E, Miginiac-Maslow M, Jaquot JP, Hirasawa M, Knaff DB, Lancelin JM
Title The 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.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 9837927
Journal J Biol Chem
Year 1998
Volume 273
Pages 33482-8
Authors Ruelland E, Johansson K, Decottignies P, Djukic N, Miginiac-Maslow M
Title The autoinhibition of sorghum NADP malate dehydrogenase is mediated by a C-terminal negative charge.
Related PDB
Related UniProtKB
[16]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
Medline ID
PubMed ID 10194350
Journal Biochemistry
Year 1999
Volume 38
Pages 4319-26
Authors Johansson K, Ramaswamy S, Saarinen M, Lemaire-Chamley M, Issakidis-Bourguet E, Miginiac-Maslow M, Eklund H
Title Structural basis for light activation of a chloroplast enzyme: the structure of sorghum NADP-malate dehydrogenase in its oxidized form.
Related PDB 7mdh
Related UniProtKB P17606
[17]
Resource
Comments
Medline ID
PubMed ID 10574915
Journal J Biol Chem
Year 1999
Volume 274
Pages 34539-42
Authors Krimm I, Goyer A, Issakidis-Bourguet E, Miginiac-Maslow M, Lancelin JM
Title Direct NMR observation of the thioredoxin-mediated reduction of the chloroplast NADP-malate dehydrogenase provides a structural basis for the relief of autoinhibition.
Related PDB
Related UniProtKB
[18]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
Medline ID
PubMed ID 10196131
Journal Structure Fold Des
Year 1999
Volume 7
Pages 461-75
Authors Carr PD, Verger D, Ashton AR, Ollis DL
Title Chloroplast NADP-malate dehydrogenase: structural basis of light-dependent regulation of activity by thiol oxidation and reduction.
Related PDB 1civ
Related UniProtKB P46489
[19]
Resource
Comments
Medline ID
PubMed ID 10913357
Journal Biochem Biophys Res Commun
Year 2000
Volume 274
Pages 440-4
Authors Yang Z, Batra R, Floyd DL, Hung HC, Chang GG, Tong L
Title Potent and competitive inhibition of malic enzymes by lanthanide ions.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 10767431
Journal FEBS Lett
Year 2000
Volume 471
Pages 240-4
Authors Schepens I, Decottignies P, Ruelland E, Johansson K, Miginiac-Maslow M
Title The dimer contact area of sorghum NADP-malate dehydrogenase: role of aspartate 101 in dimer stability and catalytic activity.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 10801830
Journal J Biol Chem
Year 2000
Volume 275
Pages 20996-1001
Authors Schepens I, Johansson K, Decottignies P, Gillibert M, Hirasawa M, Knaff DB, Miginiac-Maslow M
Title Inhibition of the thioredoxin-dependent activation of the NADP-malate dehydrogenase and cofactor specificity.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 10958800
Journal J Biol Chem
Year 2000
Volume 275
Pages 35792-8
Authors Schepens I, Ruelland E, Miginiac-Maslow M, Le Marechal P, Decottignies P
Title The role of active site arginines of sorghum NADP-malate dehydrogenase in thioredoxin-dependent activation and activity.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 11025545
Journal Proteins
Year 2000
Volume 41
Pages 334-49
Authors Lancelin JM, Guilhaudis L, Krimm I, Blackledge MJ, Marion D, Jacquot JP
Title NMR structures of thioredoxin m from the green alga Chlamydomonas reinhardtii.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 11172800
Journal FEBS Lett
Year 2001
Volume 490
Pages 1-6
Authors Drincovich MF, Casati P, Andreo CS
Title NADP-malic enzyme from plants: a ubiquitous enzyme involved in different metabolic pathways.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 11576537
Journal FEBS Lett
Year 2001
Volume 505
Pages 405-8
Authors Goyer A, Decottignies P, Issakidis-Bourguet E, Miginiac-Maslow M
Title Sites of interaction of thioredoxin with sorghum NADP-malate dehydrogenase.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 12562758
Journal J Biol Chem
Year 2003
Volume 278
Pages 13757-64
Authors Detarsio E, Wheeler MC, Campos Bermudez VA, Andreo CS, Drincovich MF
Title Maize C4 NADP-malic enzyme. Expression in Escherichia coli and characterization of site-directed mutants at the putative nucleoside-binding sites.
Related PDB
Related UniProtKB

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.

Created Updated
2004-03-16 2009-02-26