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)
3.40.50.720 : 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
3.90.110.10 : L-2-Hydroxyisocaproate Dehydrogenase; Chain A, domain 2	D00005 D00008 D00827

CATH domain

Related DB codes (homologues)

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

3.90.110.10 : L-2-Hydroxyisocaproate Dehydrogenase; Chain A, domain 2

D00005 D00008 D00827

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
P46489	MDHP_FLABI	(S)-malate + NADP(+) = oxaloacetate + NADPH.	Homodimer.	Plastid, chloroplast.
P17606	MDHP1_SORBI	(S)-malate + NADP(+) = oxaloacetate + NADPH.	Homodimer.	Plastid, chloroplast.

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

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 30797	18009 18009	30744 30744	16474 16474	15378 15378
PubChem	222656 222656	5886 5886	970 970	5884 5884	1038 1038

1civA01	Unbound	Bound:NAP	Unbound	Unbound
7mdhA01	Unbound	Unbound	Unbound	Unbound
7mdhB01	Unbound	Unbound	Unbound	Unbound
7mdhC01	Unbound	Unbound	Unbound	Unbound
7mdhD01	Unbound	Unbound	Unbound	Unbound
1civA02	Unbound	Unbound	Unbound	Unbound
7mdhA02	Unbound	Unbound	Unbound	Unbound
7mdhB02	Unbound	Unbound	Unbound	Unbound
7mdhC02	Unbound	Unbound	Unbound	Unbound
7mdhD02	Unbound	Unbound	Unbound	Unbound
1civA03	Unbound	Unbound	Unbound	Unbound
7mdhA03	Unbound	Unbound	Unbound	Unbound
7mdhB03	Unbound	Unbound	Unbound	Unbound
7mdhC03	Unbound	Unbound	Unbound	Unbound
7mdhD03	Unbound	Unbound	Unbound	Unbound
1civA04	Unbound	Unbound	Unbound	Unbound
7mdhA04	Unbound	Unbound	Unbound	Unbound
7mdhB04	Unbound	Unbound	Unbound	Unbound
7mdhC04	Unbound	Unbound	Unbound	Unbound
7mdhD04	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
7mdhA01
7mdhB01
7mdhC01
7mdhD01
1civA02	ASP 197;HIS 225;CYS 361
7mdhA02	ASP 201;HIS 229;CYS 365
7mdhB02	ASP 201;HIS 229;CYS 365
7mdhC02	ASP 201;HIS 229;CYS 365
7mdhD02	ASP 201;HIS 229;CYS 365
1civA03	CYS 20;CYS 25
7mdhA03	CYS 24;CYS 29
7mdhB03	CYS 24;CYS 29
7mdhC03	CYS 24;CYS 29
7mdhD03	CYS 24;CYS 29
1civA04	CYS 373
7mdhA04	CYS 377
7mdhB04	CYS 377
7mdhC04	CYS 377
7mdhD04	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