Reviewed, UniProtKB/Swiss-Prot P08200 (IDH_ECOLI)

Names and origin

Protein names

Recommended name:
    Isocitrate dehydrogenase [NADP]
      Short name=IDH
    EC=1.1.1.42
Alternative name(s):
    Oxalosuccinate decarboxylase
    NADP(+)-specific ICDH
    IDP

Gene names

Name:	icd
Synonyms:	icdA, icdE
Ordered Locus Names:	b1136, JW1122

Organism

Escherichia coli (strain K12) [Complete proteome] [HAMAP]

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia

Protein attributes

Sequence length	416 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	Isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH. Oxalosuccinate + NADP+ = 2-oxoglutarate + CO2 + NADPH.
Cofactor	Binds 1 magnesium or manganese ion per subunit.
Enzyme regulation	Inhibition of this enzyme by phosphorylation regulates the branch point between the Krebs cycle and the glyoxylate bypass, which is an alternate route that accumulates carbon for biosynthesis when acetate is the sole carbon source for growth.
Subunit structure	Homodimer. Ref.11
Post-translational modification	Phosphorylation state of this enzyme is controlled by isocitrate dehydrogenase kinase/phosphatase (aceK).
Sequence similarities	Belongs to the isocitrate and isopropylmalate dehydrogenases family.
Biophysicochemical properties	Kinetic parameters: KM=11.4 µM for isocitrate Ref.7

Ontologies

Keywords
Biological process	Glyoxylate bypass Tricarboxylic acid cycle
Ligand	Magnesium Manganese Metal-binding NADP
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	glyoxylate cycle Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW tricarboxylic acid cycle Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	NAD or NADH binding Inferred from electronic annotation. Source: InterPro isocitrate dehydrogenase (NADP+) activity Inferred from electronic annotation. Source: EC magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 416

416

Isocitrate dehydrogenase [NADP]

PRO_0000083551

Regions

Nucleotide binding

339 – 345

7

NADP

Sites

Metal binding

307

1

Magnesium or manganese

Binding site

104

1

NADP

Binding site

113

1

Substrate Ref.1

Binding site

115

1

Substrate

Binding site

119

1

Substrate

Binding site

129

1

Substrate

Binding site

153

1

Substrate

Binding site

352

1

NADP; via amide nitrogen and carbonyl oxygen

Binding site

391

1

NADP

Binding site

395

1

NADP

Site

160

1

Critical for catalysis

Site

230

1

Critical for catalysis

Amino acid modifications

Modified residue

113

1

Phosphoserine Ref.9

Modified residue

142

1

N6-acetyllysine Ref.8

Experimental info

Mutagenesis

113

1

S → D or E: Reduced affinity for isocitrate. Ref.9

Mutagenesis

160

1

Y → F: Large decrease in activity and a small increase in substrate affinity. Ref.7 Ref.10

Mutagenesis

230

1

K → M: Decrease in activity and substrate affinity. Ref.7 Ref.10

Secondary structure

1

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416

Helix Strand Turn

Details...

Beta strand

15 – 17

3

Beta strand

20 – 22

3

Beta strand

25 – 32

8

Helix

38 – 57

20

Beta strand

64 – 67

4

Helix

72 – 78

7

Helix

86 – 95

10

Beta strand

96 – 100

5

Beta strand

107 – 109

3

Helix

114 – 121

8

Beta strand

126 – 132

7

Beta strand

140 – 142

3

Helix

144 – 146

3

Beta strand

148 – 154

7

Helix

159 – 161

3

Helix

170 – 181

12

Beta strand

194 – 202

9

Helix

203 – 219

17

Beta strand

223 – 229

7

Turn

231 – 233

3

Turn

235 – 237

3

Helix

238 – 253

16

Beta strand

264 – 267

4

Turn

269 – 271

3

Beta strand

274 – 281

8

Helix

282 – 291

10

Helix

293 – 295

3

Beta strand

298 – 301

4

Helix

303 – 316

14

Turn

320 – 322

3

Beta strand

326 – 328

3

Beta strand

333 – 336

4

Turn

343 – 347

5

Helix

354 – 366

13

Helix

370 – 385

16

Helix

391 – 394

4

Helix

405 – 414

10

Sequences

	Sequence		Length	Mass (Da)
	P08200-1 [UniParc]. Last modified August 1, 1988. Version 1. Checksum: 9A02E707C3B4FDD9	FASTA	416	45,757
	10 20 30 40 50 60 MESKVVVPAQ GKKITLQNGK LNVPENPIIP YIEGDGIGVD VTPAMLKVVD AAVEKAYKGE 70 80 90 100 110 120 RKISWMEIYT GEKSTQVYGQ DVWLPAETLD LIREYRVAIK GPLTTPVGGG IRSLNVALRQ 130 140 150 160 170 180 ELDLYICLRP VRYYQGTPSP VKHPELTDMV IFRENSEDIY AGIEWKADSA DAEKVIKFLR 190 200 210 220 230 240 EEMGVKKIRF PEHCGIGIKP CSEEGTKRLV RAAIEYAIAN DRDSVTLVHK GNIMKFTEGA 250 260 270 280 290 300 FKDWGYQLAR EEFGGELIDG GPWLKVKNPN TGKEIVIKDV IADAFLQQIL LRPAEYDVIA 310 320 330 340 350 360 CMNLNGDYIS DALAAQVGGI GIAPGANIGD ECALFEATHG TAPKYAGQDK VNPGSIILSA 370 380 390 400 410 EMMLRHMGWT EAADLIVKGM EGAINAKTVT YDFERLMDGA KLLKCSEFGD AIIENM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Inactivation of isocitrate dehydrogenase by phosphorylation is mediated by the negative charge of the phosphate." Thorsness P.E., Koshland D.E. Jr. J. Biol. Chem. 262:10422-10425(1987) [PubMed: 3112144] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 12.7-28.0 min region on the linkage map." Oshima T., Aiba H., Baba T., Fujita K., Hayashi K., Honjo A., Ikemoto K., Inada T., Itoh T., Kajihara M., Kanai K., Kashimoto K., Kimura S., Kitagawa M., Makino K., Masuda S., Miki T., Mizobuchi K. , Mori H., Motomura K., Nakamura Y., Nashimoto H., Nishio Y., Saito N., Sampei G., Seki Y., Tagami H., Takemoto K., Wada C., Yamamoto Y., Yano M., Horiuchi T. DNA Res. 3:137-155(1996) [PubMed: 8905232] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[3]	"The complete genome sequence of Escherichia coli K-12." Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y. Science 277:1453-1474(1997) [PubMed: 9278503] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[4]	"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T. Mol. Syst. Biol. 2:E1-E5(2006) [PubMed: 16738553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[5]	"Evolutionary genetics of the isocitrate dehydrogenase gene (icd) in Escherichia coli and Salmonella enterica." Wang F.-S., Whittam T.S., Selander R.K. J. Bacteriol. 179:6551-6559(1997) [PubMed: 9352899] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 11-414. Strain: CH734.
[6]	"Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12." Link A.J., Robison K., Church G.M. Electrophoresis 18:1259-1313(1997) [PubMed: 9298646] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-12. Strain: K12 / EMG2.
[7]	"Mutational analysis of the catalytic residues lysine 230 and tyrosine 160 in the NADP(+)-dependent isocitrate dehydrogenase from Escherichia coli." Lee M.E., Dyer D.H., Klein O.D., Bolduc J.M., Stoddard B.L., Koshland D.E. Jr. Biochemistry 34:378-384(1995) [PubMed: 7819221] [Abstract] Cited for: ENZYME KINETICS, MUTAGENESIS OF TYR-160 AND LYS-230.
[8]	"Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli." Zhang J., Sprung R., Pei J., Tan X., Kim S., Zhu H., Liu C.F., Grishin N.V., Zhao Y. Mol. Cell. Proteomics 8:215-225(2009) [PubMed: 18723842] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-142, MASS SPECTROMETRY.
[9]	"Regulation of an enzyme by phosphorylation at the active site." Hurley J.H., Dean A.M., Sohl J.L., Koshland D.E. Jr., Stroud R.M. Science 249:1012-1016(1990) [PubMed: 2204109] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH ISOCITRATE AND MAGNESIUM, PHOSPHORYLATION AT SER-113, MUTAGENESIS OF SER-113.
[10]	"Mutagenesis and Laue structures of enzyme intermediates: isocitrate dehydrogenase." Bolduc J.M., Dyer D.H., Scott W.G., Singer P., Sweet R.M., Koshland D.E. Jr., Stoddard B.L. Science 268:1312-1318(1995) [PubMed: 7761851] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH ISOCITRATE; NADP AND MAGNESIUM, MUTAGENESIS OF TYR-160 AND LYS-230, BIOPHYSICOCHEMICAL PROPERTIES.
[11]	"Structure of a bacterial enzyme regulated by phosphorylation, isocitrate dehydrogenase." Hurley J.H., Thorsness P.E., Ramalingam V., Helmers N.H., Koshland D.E. Jr., Stroud R.M. Proc. Natl. Acad. Sci. U.S.A. 86:8635-8639(1989) [PubMed: 2682654] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH NADP, SUBUNIT.
[12]	"Active site water molecules revealed in the 2.1 A resolution structure of a site-directed mutant of isocitrate dehydrogenase." Cherbavaz D.B., Lee M.E., Stroud R.M., Koshland D.E. Jr. J. Mol. Biol. 295:377-385(2000) [PubMed: 10623532] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF MUTANT MET-230.
[13]	"Structural basis for a change in substrate specificity: crystal structure of S113E isocitrate dehydrogenase in a complex with isopropylmalate, Mg2+, and NADP." Doyle S.A., Beernink P.T., Koshland D.E. Jr. Biochemistry 40:4234-4241(2001) [PubMed: 11284679] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF MUTANT GLU-113 IN COMPLEX WITH SUBSTRATE ANALOG; MAGNESIUM AND NADP.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J02799 Genomic DNA. Translation: AAA24006.1.
U00096 Genomic DNA. Translation: AAC74220.1.
AP009048 Genomic DNA. Translation: BAA35958.1.
AF017587 Genomic DNA. Translation: AAC45887.1.

PIR

DCECIS. A28482.

RefSeq

AP_001762.1.
NP_415654.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AI2	X-ray	1.90	A	1-416	[»]
1AI3	X-ray	1.90	A	1-416	[»]
1BL5	X-ray	2.50	A	3-416	[»]
1CW1	X-ray	2.10	A	1-416	[»]
1CW4	X-ray	2.10	A	1-416	[»]
1CW7	X-ray	2.60	A	1-416	[»]
1GRO	X-ray	2.50	A	1-416	[»]
1GRP	X-ray	2.50	A	1-416	[»]
1HJ6	X-ray	2.00	A	1-416	[»]
1IDC	X-ray	2.50	A	1-416	[»]
1IDD	X-ray	2.50	A	1-416	[»]
1IDE	X-ray	2.50	A	1-416	[»]
1IDF	X-ray	2.50	A	1-416	[»]
1IKA	X-ray	2.70	A	1-416	[»]
1ISO	X-ray	1.90	A	1-416	[»]
1P8F	X-ray	1.85	A	1-416	[»]
1PB1	X-ray	1.70	A	1-416	[»]
1PB3	X-ray	1.70	A	1-416	[»]
1SJS	X-ray	2.42	A	1-416	[»]
3ICD	X-ray	2.50	A	1-416	[»]
4ICD	X-ray	2.50	A	1-416	[»]
5ICD	X-ray	2.50	A	1-416	[»]
6ICD	X-ray	2.80	A	1-416	[»]
7ICD	X-ray	2.40	A	1-416	[»]
8ICD	X-ray	2.50	A	1-416	[»]
9ICD	X-ray	2.50	A	1-416	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P08200.

PTM databases

PhosSite

P08200.

2-D gel databases

SWISS-2DPAGE

P08200.

2DBase-Ecoli

P08200.

ECO2DBASE

C043.8. 6TH EDITION.

Genome annotation databases

GeneID

945702.

GenomeReviews

Gene locus JW1122 in contig AP009048_GR.
Gene locus b1136 in contig U00096_GR.

KEGG

ecj:JW1122.
eco:b1136.

Organism-specific databases

EchoBASE

EB0484.

EcoGene

EG10489. icd.
EG10009. icdC.

CMR

Search...

Phylogenomic databases

eggNOG

COG0538.

HOGENOM

HBG518924.

OMA

RDWGYEL.

Enzyme and pathway databases

BioCyc

EcoCyc:ISOCITDEH-SUBUNIT.
ECOL168927:B1136-MONOMER.
MetaCyc:ISOCITDEH-SUBUNIT.

Gene expression databases

Genevestigator

P08200.

Family and domain databases

InterPro

IPR019818. IsoCit/isopropylmalate_DH_CS.
IPR001804. Isocitrate/isopropylmalate_DH.
IPR004439. Isocitrate_DH_NADP_prok.
[Graphical view]

Gene3D

G3DSA:3.40.718.10. IDH_IMDH. 1 hit.

PANTHER

PTHR11835. IDH_IMDH_dimeric. 1 hit.

Pfam

PF00180. Iso_dh. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00183. prok_nadp_idh. 1 hit.

PROSITE

PS00470. IDH_IMDH. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

IDH_ECOLI

Accession

Primary (citable) accession number: P08200

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	August 1, 1988
Last modified:	February 9, 2010
This is version 104 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HAMAP (High-quality Automated and Manual Annotation of microbial Proteomes)