P08200 (IDH_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Isocitrate dehydrogenase [NADP]
Short name=IDH
EC=1.1.1.42

Alternative name(s):
IDP
NADP(+)-specific ICDH
Oxalosuccinate decarboxylase

Gene names

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

Organism

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

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia › Escherichia coli

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. Ref.10
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.13
Post-translational modification	Phosphorylation state of this enzyme is controlled by isocitrate dehydrogenase kinase/phosphatase (AceK). Succinylation probably inhibits enzymatic activity. Ref.10
Sequence similarities	Belongs to the isocitrate and isopropylmalate dehydrogenases family.
Biophysicochemical properties	Kinetic parameters: KM=11.4 µM for isocitrate Ref.7 Ref.12

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 Reference proteome
Gene Ontology (GO)
Biological_process	electron transport chain Inferred from mutant phenotype PubMed 776950. Source: EcoliWiki glyoxylate cycle Inferred from electronic annotation. Source: UniProtKB-KW tricarboxylic acid cycle Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay PubMed 34215. Source: EcoliWiki
Molecular_function	NAD binding Inferred from electronic annotation. Source: InterPro isocitrate dehydrogenase (NADP+) activity Inferred from direct assay Ref.10. Source: UniProtKB magnesium ion binding Inferred from electronic annotation. Source: InterPro
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

100

1

N6-succinyllysine Ref.10

Modified residue

113

1

Phosphoserine Ref.11

Modified residue

142

1

N6-acetyllysine Ref.9

Modified residue

242

1

N6-succinyllysine Ref.10

Experimental info

Mutagenesis

100

1

K → R or E: Abolishes enzymatic activity. Ref.10

Mutagenesis

113

1

S → D or E: Reduced affinity for isocitrate. Ref.11

Mutagenesis

160

1

Y → F: Large decrease in activity and a small increase in substrate affinity. Ref.7 Ref.12

Mutagenesis

230

1

K → M: Decrease in activity and substrate affinity. Ref.7 Ref.12

Mutagenesis

242

1

K → E: Strongly impairs enzymatic activity. Ref.10

Mutagenesis

242

1

K → R: Impairs enzymatic activity. 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

58 – 61

4

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

158 – 161

4

Beta strand

163 – 165

3

Helix

170 – 181

12

Beta strand

196 – 198

3

Helix

203 – 219

17

Beta strand

223 – 229

7

Turn

231 – 233

3

Turn

235 – 237

3

Helix

238 – 253

16

Beta strand

256 – 258

3

Beta strand

259 – 262

4

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

Helix

343 – 345

3

Turn

346 – 349

4

Helix

354 – 366

13

Helix

370 – 385

16

Beta strand

388 – 390

3

Helix

391 – 394

4

Beta strand

397 – 399

3

Beta strand

401 – 403

3

Helix

405 – 414

10

Sequences

	Sequence		Length	Mass (Da)
	P08200 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: ENZYME KINETICS, MUTAGENESIS OF TYR-160 AND LYS-230.
[8]	"Escherichia coli proteome analysis using the gene-protein database." VanBogelen R.A., Abshire K.Z., Moldover B., Olson E.R., Neidhardt F.C. Electrophoresis 18:1243-1251(1997) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY 2D-GEL.
[9]	"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] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-142, MASS SPECTROMETRY. Strain: K12 / JW1106 and K12 / MG1655 / ATCC 47076.
[10]	"Identification of lysine succinylation as a new post-translational modification." Zhang Z., Tan M., Xie Z., Dai L., Chen Y., Zhao Y. Nat. Chem. Biol. 7:58-63(2011) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, SUCCINYLATION AT LYS-100 AND LYS-242, MUTAGENESIS OF LYS-100 AND LYS-242. Strain: K12.
[11]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH ISOCITRATE AND MAGNESIUM, PHOSPHORYLATION AT SER-113, MUTAGENESIS OF SER-113.
[12]	"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] [Europe PMC] [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.
[13]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH NADP, SUBUNIT.
[14]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF MUTANT MET-230.
[15]	"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] [Europe PMC] [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

NP_415654.1. NC_000913.2.
YP_489404.1. NC_007779.1.

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	[»]
3LCB	X-ray	2.90	C/D	1-416	[»]
4AJ3	X-ray	1.90	A	1-416	[»]
4AJA	X-ray	1.80	A	1-416	[»]
4AJB	X-ray	1.90	A	1-416	[»]
4AJC	X-ray	2.30	A	1-416	[»]
4AJR	X-ray	2.69	A	1-416	[»]
4AJS	X-ray	1.80	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	[»]

ProteinModelPortal

P08200.

SMR

P08200. Positions 1-416.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-10006N.

IntAct

P08200. 5 interactions.

STRING

511145.b1136.

PTM databases

PhosSite

P010427.

2D gel databases

SWISS-2DPAGE

P08200.

Proteomic databases

PaxDb

P08200.

PRIDE

P08200.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAC74220; AAC74220; b1136.
BAA35958; BAA35958; BAA35958.

GeneID

12934062.
945702.

KEGG

ecj:Y75_p1106.
eco:b1136.

PATRIC

32117521. VBIEscCol129921_1183.

Organism-specific databases

EchoBASE

EB0484.

EcoGene

EG10489. icd.
EG10009. icdC.

Phylogenomic databases

eggNOG

COG0538.

HOGENOM

HOG000021113.

KO

K00031.

OMA

FRDWGYE.

ProtClustDB

PRK07006.

Enzyme and pathway databases

BioCyc

EcoCyc:ISOCITDEH-SUBUNIT.
ECOL316407:JW1122-MONOMER.
MetaCyc:ISOCITDEH-SUBUNIT.

SABIO-RK

P08200.

Gene expression databases

Genevestigator

P08200.

Family and domain databases

Gene3D

3.40.718.10. 1 hit.

InterPro

IPR019818. IsoCit/isopropylmalate_DH_CS.
IPR001804. Isocitrate/isopropylmalate_DH.
IPR004439. Isocitrate_DH_NADP_dimer_prok.
IPR024084. IsoPropMal-DH-like_dom.
[Graphical view]

PANTHER

PTHR11835. PTHR11835. 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...

Other

EvolutionaryTrace

P08200.

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:	May 1, 2013
This is version 136 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program