ID IDH_ECOLI Reviewed; 416 AA.
AC P08200;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1988, sequence version 1.
DT 24-JAN-2024, entry version 197.
DE RecName: Full=Isocitrate dehydrogenase [NADP];
DE Short=IDH;
DE EC=1.1.1.42 {ECO:0000269|PubMed:21151122, ECO:0000269|PubMed:3112144, ECO:0000269|PubMed:7761851, ECO:0000269|PubMed:7819221};
DE AltName: Full=IDP;
DE AltName: Full=NADP(+)-specific ICDH;
DE AltName: Full=Oxalosuccinate decarboxylase;
GN Name=icd; Synonyms=icdA, icdE; OrderedLocusNames=b1136, JW1122;
OS Escherichia coli (strain K12).
OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP AND MUTAGENESIS OF SER-113.
RX PubMed=3112144; DOI=10.1016/s0021-9258(18)60975-5;
RA Thorsness P.E., Koshland D.E. Jr.;
RT "Inactivation of isocitrate dehydrogenase by phosphorylation is mediated by
RT the negative charge of the phosphate.";
RL J. Biol. Chem. 262:10422-10425(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=8905232; DOI=10.1093/dnares/3.3.137;
RA Oshima T., Aiba H., Baba T., Fujita K., Hayashi K., Honjo A., Ikemoto K.,
RA Inada T., Itoh T., Kajihara M., Kanai K., Kashimoto K., Kimura S.,
RA Kitagawa M., Makino K., Masuda S., Miki T., Mizobuchi K., Mori H.,
RA Motomura K., Nakamura Y., Nashimoto H., Nishio Y., Saito N., Sampei G.,
RA Seki Y., Tagami H., Takemoto K., Wada C., Yamamoto Y., Yano M.,
RA Horiuchi T.;
RT "A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT the 12.7-28.0 min region on the linkage map.";
RL DNA Res. 3:137-155(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 11-414.
RC STRAIN=CH734;
RX PubMed=9352899; DOI=10.1128/jb.179.21.6551-6559.1997;
RA Wang F.-S., Whittam T.S., Selander R.K.;
RT "Evolutionary genetics of the isocitrate dehydrogenase gene (icd) in
RT Escherichia coli and Salmonella enterica.";
RL J. Bacteriol. 179:6551-6559(1997).
RN [6]
RP PROTEIN SEQUENCE OF 1-12.
RC STRAIN=K12 / EMG2;
RX PubMed=9298646; DOI=10.1002/elps.1150180807;
RA Link A.J., Robison K., Church G.M.;
RT "Comparing the predicted and observed properties of proteins encoded in the
RT genome of Escherichia coli K-12.";
RL Electrophoresis 18:1259-1313(1997).
RN [7]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF
RP TYR-160 AND LYS-230.
RX PubMed=7819221; DOI=10.1021/bi00001a046;
RA Lee M.E., Dyer D.H., Klein O.D., Bolduc J.M., Stoddard B.L.,
RA Koshland D.E. Jr.;
RT "Mutational analysis of the catalytic residues lysine 230 and tyrosine 160
RT in the NADP(+)-dependent isocitrate dehydrogenase from Escherichia coli.";
RL Biochemistry 34:378-384(1995).
RN [8]
RP IDENTIFICATION BY 2D-GEL.
RX PubMed=9298644; DOI=10.1002/elps.1150180805;
RA VanBogelen R.A., Abshire K.Z., Moldover B., Olson E.R., Neidhardt F.C.;
RT "Escherichia coli proteome analysis using the gene-protein database.";
RL Electrophoresis 18:1243-1251(1997).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-142, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=K12 / JW1106, and K12 / MG1655 / ATCC 47076;
RX PubMed=18723842; DOI=10.1074/mcp.m800187-mcp200;
RA Zhang J., Sprung R., Pei J., Tan X., Kim S., Zhu H., Liu C.F.,
RA Grishin N.V., Zhao Y.;
RT "Lysine acetylation is a highly abundant and evolutionarily conserved
RT modification in Escherichia coli.";
RL Mol. Cell. Proteomics 8:215-225(2009).
RN [10]
RP CATALYTIC ACTIVITY, SUCCINYLATION AT LYS-100 AND LYS-242, AND MUTAGENESIS
RP OF LYS-100 AND LYS-242.
RC STRAIN=K12;
RX PubMed=21151122; DOI=10.1038/nchembio.495;
RA Zhang Z., Tan M., Xie Z., Dai L., Chen Y., Zhao Y.;
RT "Identification of lysine succinylation as a new post-translational
RT modification.";
RL Nat. Chem. Biol. 7:58-63(2011).
RN [11] {ECO:0007744|PDB:3ICD}
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH NADP, AND SUBUNIT.
RX PubMed=2682654; DOI=10.1073/pnas.86.22.8635;
RA Hurley J.H., Thorsness P.E., Ramalingam V., Helmers N.H.,
RA Koshland D.E. Jr., Stroud R.M.;
RT "Structure of a bacterial enzyme regulated by phosphorylation, isocitrate
RT dehydrogenase.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:8635-8639(1989).
RN [12] {ECO:0007744|PDB:5ICD, ECO:0007744|PDB:6ICD, ECO:0007744|PDB:7ICD, ECO:0007744|PDB:8ICD}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEX WITH ISOCITRATE AND
RP MAGNESIUM, PHOSPHORYLATION AT SER-113, AND MUTAGENESIS OF SER-113.
RX PubMed=2204109; DOI=10.1126/science.2204109;
RA Hurley J.H., Dean A.M., Sohl J.L., Koshland D.E. Jr., Stroud R.M.;
RT "Regulation of an enzyme by phosphorylation at the active site.";
RL Science 249:1012-1016(1990).
RN [13] {ECO:0007744|PDB:1IDC, ECO:0007744|PDB:1IDD, ECO:0007744|PDB:1IDE, ECO:0007744|PDB:1IDF}
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH ISOCITRATE; NADP AND
RP MAGNESIUM, MUTAGENESIS OF TYR-160 AND LYS-230, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND CATALYTIC ACTIVITY.
RX PubMed=7761851; DOI=10.1126/science.7761851;
RA Bolduc J.M., Dyer D.H., Scott W.G., Singer P., Sweet R.M.,
RA Koshland D.E. Jr., Stoddard B.L.;
RT "Mutagenesis and Laue structures of enzyme intermediates: isocitrate
RT dehydrogenase.";
RL Science 268:1312-1318(1995).
RN [14] {ECO:0007744|PDB:1CW1, ECO:0007744|PDB:1CW4, ECO:0007744|PDB:1CW7}
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF MUTANT MET-230.
RX PubMed=10623532; DOI=10.1006/jmbi.1999.3195;
RA Cherbavaz D.B., Lee M.E., Stroud R.M., Koshland D.E. Jr.;
RT "Active site water molecules revealed in the 2.1 A resolution structure of
RT a site-directed mutant of isocitrate dehydrogenase.";
RL J. Mol. Biol. 295:377-385(2000).
RN [15] {ECO:0007744|PDB:1HJ6}
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF MUTANT GLU-113 IN COMPLEX WITH
RP SUBSTRATE ANALOG; MAGNESIUM AND NADP.
RX PubMed=11284679; DOI=10.1021/bi002533q;
RA Doyle S.A., Beernink P.T., Koshland D.E. Jr.;
RT "Structural basis for a change in substrate specificity: crystal structure
RT of S113E isocitrate dehydrogenase in a complex with isopropylmalate, Mg2+,
RT and NADP.";
RL Biochemistry 40:4234-4241(2001).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-threo-isocitrate + NADP(+) = 2-oxoglutarate + CO2 + NADPH;
CC Xref=Rhea:RHEA:19629, ChEBI:CHEBI:15562, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.42;
CC Evidence={ECO:0000269|PubMed:21151122, ECO:0000269|PubMed:3112144,
CC ECO:0000269|PubMed:7761851, ECO:0000269|PubMed:7819221};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:7761851};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit.
CC {ECO:0000269|PubMed:11284679, ECO:0000269|PubMed:7761851};
CC -!- ACTIVITY REGULATION: Inhibition of this enzyme by phosphorylation
CC regulates the branch point between the Krebs cycle and the glyoxylate
CC bypass, which is an alternate route that accumulates carbon for
CC biosynthesis when acetate is the sole carbon source for growth.
CC {ECO:0000305|PubMed:3112144}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=11.4 uM for isocitrate {ECO:0000269|PubMed:7819221};
CC KM=13 uM for isocitrate {ECO:0000269|PubMed:7761851};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11284679,
CC ECO:0000269|PubMed:2204109, ECO:0000269|PubMed:2682654,
CC ECO:0000269|PubMed:7761851}.
CC -!- INTERACTION:
CC P08200; P11071: aceK; NbExp=5; IntAct=EBI-369069, EBI-1112800;
CC -!- PTM: Phosphorylation state of this enzyme is controlled by isocitrate
CC dehydrogenase kinase/phosphatase (AceK). {ECO:0000269|PubMed:2204109}.
CC -!- PTM: Succinylation probably inhibits enzymatic activity.
CC {ECO:0000269|PubMed:21151122}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. {ECO:0000305}.
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DR EMBL; J02799; AAA24006.1; -; Genomic_DNA.
DR EMBL; U00096; AAC74220.1; -; Genomic_DNA.
DR EMBL; AP009048; BAA35958.1; -; Genomic_DNA.
DR EMBL; AF017587; AAC45887.1; -; Genomic_DNA.
DR PIR; A28482; DCECIS.
DR RefSeq; NP_415654.1; NC_000913.3.
DR RefSeq; WP_000444484.1; NZ_CP064683.1.
DR PDB; 1AI2; X-ray; 1.90 A; A=1-416.
DR PDB; 1AI3; X-ray; 1.90 A; A=1-416.
DR PDB; 1BL5; X-ray; 2.50 A; A=3-416.
DR PDB; 1CW1; X-ray; 2.10 A; A=1-416.
DR PDB; 1CW4; X-ray; 2.10 A; A=1-416.
DR PDB; 1CW7; X-ray; 2.60 A; A=1-416.
DR PDB; 1GRO; X-ray; 2.50 A; A=1-416.
DR PDB; 1GRP; X-ray; 2.50 A; A=1-416.
DR PDB; 1HJ6; X-ray; 2.00 A; A=1-416.
DR PDB; 1IDC; X-ray; 2.50 A; A=1-416.
DR PDB; 1IDD; X-ray; 2.50 A; A=1-416.
DR PDB; 1IDE; X-ray; 2.50 A; A=1-416.
DR PDB; 1IDF; X-ray; 2.50 A; A=1-416.
DR PDB; 1IKA; X-ray; 2.70 A; A=1-416.
DR PDB; 1ISO; X-ray; 1.90 A; A=1-416.
DR PDB; 1P8F; X-ray; 1.85 A; A=1-416.
DR PDB; 1PB1; X-ray; 1.70 A; A=1-416.
DR PDB; 1PB3; X-ray; 1.70 A; A=1-416.
DR PDB; 1SJS; X-ray; 2.42 A; A=1-416.
DR PDB; 3ICD; X-ray; 2.50 A; A=1-416.
DR PDB; 3LCB; X-ray; 2.90 A; C/D=1-416.
DR PDB; 4AJ3; X-ray; 1.90 A; A=1-416.
DR PDB; 4AJA; X-ray; 1.80 A; A=1-416.
DR PDB; 4AJB; X-ray; 1.90 A; A=1-416.
DR PDB; 4AJC; X-ray; 2.30 A; A=1-416.
DR PDB; 4AJR; X-ray; 2.69 A; A=1-416.
DR PDB; 4AJS; X-ray; 1.80 A; A=1-416.
DR PDB; 4BNP; X-ray; 2.00 A; A=1-416.
DR PDB; 4ICD; X-ray; 2.50 A; A=1-416.
DR PDB; 4P69; X-ray; 3.30 A; C/D=2-416.
DR PDB; 5ICD; X-ray; 2.50 A; A=1-416.
DR PDB; 6ICD; X-ray; 2.80 A; A=1-416.
DR PDB; 7ICD; X-ray; 2.40 A; A=1-416.
DR PDB; 8ICD; X-ray; 2.50 A; A=1-416.
DR PDB; 9ICD; X-ray; 2.50 A; A=1-416.
DR PDBsum; 1AI2; -.
DR PDBsum; 1AI3; -.
DR PDBsum; 1BL5; -.
DR PDBsum; 1CW1; -.
DR PDBsum; 1CW4; -.
DR PDBsum; 1CW7; -.
DR PDBsum; 1GRO; -.
DR PDBsum; 1GRP; -.
DR PDBsum; 1HJ6; -.
DR PDBsum; 1IDC; -.
DR PDBsum; 1IDD; -.
DR PDBsum; 1IDE; -.
DR PDBsum; 1IDF; -.
DR PDBsum; 1IKA; -.
DR PDBsum; 1ISO; -.
DR PDBsum; 1P8F; -.
DR PDBsum; 1PB1; -.
DR PDBsum; 1PB3; -.
DR PDBsum; 1SJS; -.
DR PDBsum; 3ICD; -.
DR PDBsum; 3LCB; -.
DR PDBsum; 4AJ3; -.
DR PDBsum; 4AJA; -.
DR PDBsum; 4AJB; -.
DR PDBsum; 4AJC; -.
DR PDBsum; 4AJR; -.
DR PDBsum; 4AJS; -.
DR PDBsum; 4BNP; -.
DR PDBsum; 4ICD; -.
DR PDBsum; 4P69; -.
DR PDBsum; 5ICD; -.
DR PDBsum; 6ICD; -.
DR PDBsum; 7ICD; -.
DR PDBsum; 8ICD; -.
DR PDBsum; 9ICD; -.
DR AlphaFoldDB; P08200; -.
DR SMR; P08200; -.
DR BioGRID; 4263056; 28.
DR BioGRID; 850074; 1.
DR DIP; DIP-10006N; -.
DR IntAct; P08200; 6.
DR STRING; 511145.b1136; -.
DR DrugBank; DB02190; (S)-oxalosuccinic acid.
DR DrugBank; DB04279; 3-Isopropylmalic Acid.
DR DrugBank; DB01727; Isocitric Acid.
DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate.
DR iPTMnet; P08200; -.
DR SWISS-2DPAGE; P08200; -.
DR jPOST; P08200; -.
DR PaxDb; 511145-b1136; -.
DR EnsemblBacteria; AAC74220; AAC74220; b1136.
DR GeneID; 945702; -.
DR KEGG; ecj:JW1122; -.
DR KEGG; eco:b1136; -.
DR PATRIC; fig|511145.12.peg.1183; -.
DR EchoBASE; EB0484; -.
DR eggNOG; COG0538; Bacteria.
DR HOGENOM; CLU_031953_7_1_6; -.
DR InParanoid; P08200; -.
DR OMA; CVRPCRY; -.
DR PhylomeDB; P08200; -.
DR BioCyc; EcoCyc:ISOCITDEH-SUBUNIT; -.
DR BioCyc; MetaCyc:ISOCITDEH-SUBUNIT; -.
DR BRENDA; 1.1.1.42; 2026.
DR BRENDA; 2.7.11.5; 2026.
DR SABIO-RK; P08200; -.
DR EvolutionaryTrace; P08200; -.
DR PRO; PR:P08200; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IDA:EcoliWiki.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0097216; F:guanosine tetraphosphate binding; IDA:EcoCyc.
DR GO; GO:0004450; F:isocitrate dehydrogenase (NADP+) activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0022900; P:electron transport chain; IMP:EcoliWiki.
DR GO; GO:0006097; P:glyoxylate cycle; IEA:UniProtKB-KW.
DR GO; GO:0006979; P:response to oxidative stress; IMP:EcoCyc.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IDA:EcoliWiki.
DR Gene3D; 3.40.718.10; Isopropylmalate Dehydrogenase; 1.
DR InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR InterPro; IPR004439; Isocitrate_DH_NADP_dimer_prok.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR NCBIfam; TIGR00183; prok_nadp_idh; 1.
DR PANTHER; PTHR43504; ISOCITRATE DEHYDROGENASE [NADP]; 1.
DR PANTHER; PTHR43504:SF1; ISOCITRATE DEHYDROGENASE [NADP]; 1.
DR Pfam; PF00180; Iso_dh; 1.
DR SMART; SM01329; Iso_dh; 1.
DR SUPFAM; SSF53659; Isocitrate/Isopropylmalate dehydrogenase-like; 1.
DR PROSITE; PS00470; IDH_IMDH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing; Glyoxylate bypass;
KW Magnesium; Manganese; Metal-binding; NADP; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Tricarboxylic acid cycle.
FT CHAIN 1..416
FT /note="Isocitrate dehydrogenase [NADP]"
FT /id="PRO_0000083551"
FT BINDING 104
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11284679,
FT ECO:0000269|PubMed:2682654, ECO:0000269|PubMed:7761851,
FT ECO:0007744|PDB:1AI2, ECO:0007744|PDB:1HJ6,
FT ECO:0007744|PDB:1IDE, ECO:0007744|PDB:4AJ3,
FT ECO:0007744|PDB:4AJR"
FT BINDING 113
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10623532,
FT ECO:0000269|PubMed:2204109, ECO:0007744|PDB:1AI3,
FT ECO:0007744|PDB:1CW1, ECO:0007744|PDB:1CW7,
FT ECO:0007744|PDB:1GRP, ECO:0007744|PDB:1P8F,
FT ECO:0007744|PDB:1PB1, ECO:0007744|PDB:4AJ3,
FT ECO:0007744|PDB:4AJA, ECO:0007744|PDB:4AJB,
FT ECO:0007744|PDB:4AJS, ECO:0007744|PDB:4BNP,
FT ECO:0007744|PDB:5ICD, ECO:0007744|PDB:8ICD"
FT BINDING 115
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10623532,
FT ECO:0000269|PubMed:2204109, ECO:0007744|PDB:1AI3,
FT ECO:0007744|PDB:1CW1, ECO:0007744|PDB:1CW7,
FT ECO:0007744|PDB:1GRP, ECO:0007744|PDB:1P8F,
FT ECO:0007744|PDB:1PB1, ECO:0007744|PDB:4AJ3,
FT ECO:0007744|PDB:4AJA, ECO:0007744|PDB:4AJB,
FT ECO:0007744|PDB:4AJS, ECO:0007744|PDB:4BNP,
FT ECO:0007744|PDB:5ICD, ECO:0007744|PDB:8ICD"
FT BINDING 119
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10623532,
FT ECO:0000269|PubMed:2204109, ECO:0007744|PDB:1AI3,
FT ECO:0007744|PDB:1CW7, ECO:0007744|PDB:1GRP,
FT ECO:0007744|PDB:1P8F, ECO:0007744|PDB:1PB1,
FT ECO:0007744|PDB:4AJ3, ECO:0007744|PDB:4AJA,
FT ECO:0007744|PDB:4AJB, ECO:0007744|PDB:4AJS,
FT ECO:0007744|PDB:4BNP, ECO:0007744|PDB:5ICD,
FT ECO:0007744|PDB:8ICD"
FT BINDING 129
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10623532,
FT ECO:0000269|PubMed:2204109, ECO:0007744|PDB:1AI3,
FT ECO:0007744|PDB:1CW1, ECO:0007744|PDB:1CW7,
FT ECO:0007744|PDB:1GRP, ECO:0007744|PDB:1P8F,
FT ECO:0007744|PDB:1PB1, ECO:0007744|PDB:4AJ3,
FT ECO:0007744|PDB:4AJA, ECO:0007744|PDB:4AJB,
FT ECO:0007744|PDB:4AJS, ECO:0007744|PDB:4BNP,
FT ECO:0007744|PDB:5ICD, ECO:0007744|PDB:8ICD"
FT BINDING 153
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10623532,
FT ECO:0000269|PubMed:2204109, ECO:0007744|PDB:1AI3,
FT ECO:0007744|PDB:1CW1, ECO:0007744|PDB:1CW7,
FT ECO:0007744|PDB:1GRP, ECO:0007744|PDB:1P8F,
FT ECO:0007744|PDB:1PB1, ECO:0007744|PDB:4AJ3,
FT ECO:0007744|PDB:4AJA, ECO:0007744|PDB:4AJB,
FT ECO:0007744|PDB:4AJS, ECO:0007744|PDB:4BNP,
FT ECO:0007744|PDB:5ICD, ECO:0007744|PDB:8ICD"
FT BINDING 307
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:11284679,
FT ECO:0000269|PubMed:2204109, ECO:0000269|PubMed:7761851,
FT ECO:0007744|PDB:1AI3, ECO:0007744|PDB:1BL5,
FT ECO:0007744|PDB:1GRP, ECO:0007744|PDB:1HJ6,
FT ECO:0007744|PDB:1IDC, ECO:0007744|PDB:1P8F,
FT ECO:0007744|PDB:4AJB, ECO:0007744|PDB:4AJR,
FT ECO:0007744|PDB:4AJS, ECO:0007744|PDB:4BNP,
FT ECO:0007744|PDB:8ICD"
FT BINDING 339..345
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11284679,
FT ECO:0000269|PubMed:2682654, ECO:0000269|PubMed:7761851,
FT ECO:0007744|PDB:1AI2, ECO:0007744|PDB:1BL5,
FT ECO:0007744|PDB:1HJ6, ECO:0007744|PDB:1IDE,
FT ECO:0007744|PDB:1ISO, ECO:0007744|PDB:4AJ3,
FT ECO:0007744|PDB:4AJR, ECO:0007744|PDB:9ICD"
FT BINDING 352
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11284679,
FT ECO:0000269|PubMed:2682654, ECO:0000269|PubMed:7761851,
FT ECO:0007744|PDB:1AI2, ECO:0007744|PDB:1BL5,
FT ECO:0007744|PDB:1HJ6, ECO:0007744|PDB:1IDE,
FT ECO:0007744|PDB:4AJ3, ECO:0007744|PDB:4AJR,
FT ECO:0007744|PDB:9ICD"
FT BINDING 391
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11284679,
FT ECO:0000269|PubMed:2682654, ECO:0000269|PubMed:7761851,
FT ECO:0007744|PDB:1AI2, ECO:0007744|PDB:1BL5,
FT ECO:0007744|PDB:1HJ6, ECO:0007744|PDB:1IDE,
FT ECO:0007744|PDB:4AJ3, ECO:0007744|PDB:4AJR,
FT ECO:0007744|PDB:9ICD"
FT BINDING 395
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11284679,
FT ECO:0000269|PubMed:2682654, ECO:0000269|PubMed:7761851,
FT ECO:0007744|PDB:1AI2, ECO:0007744|PDB:9ICD"
FT SITE 160
FT /note="Critical for catalysis"
FT /evidence="ECO:0000269|PubMed:7761851,
FT ECO:0000269|PubMed:7819221"
FT SITE 230
FT /note="Critical for catalysis"
FT /evidence="ECO:0000269|PubMed:7761851,
FT ECO:0000269|PubMed:7819221"
FT MOD_RES 100
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000269|PubMed:21151122"
FT MOD_RES 113
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:2204109,
FT ECO:0000269|PubMed:3112144"
FT MOD_RES 142
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:18723842"
FT MOD_RES 242
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000269|PubMed:21151122"
FT MUTAGEN 100
FT /note="K->R,E: Abolishes enzymatic activity."
FT /evidence="ECO:0000269|PubMed:21151122"
FT MUTAGEN 113
FT /note="S->A,T: Decreased enzyme activity. Loss of
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:3112144"
FT MUTAGEN 113
FT /note="S->D,E: Reduced affinity for isocitrate."
FT /evidence="ECO:0000269|PubMed:2204109"
FT MUTAGEN 113
FT /note="S->D: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:3112144"
FT MUTAGEN 160
FT /note="Y->F: Nearly abolishes enzyme activity. No
FT significant effect on substrate affinity."
FT /evidence="ECO:0000269|PubMed:7761851,
FT ECO:0000269|PubMed:7819221"
FT MUTAGEN 230
FT /note="K->M: Nearly abolishes enzyme activity and strongly
FT reduces substrate affinity."
FT /evidence="ECO:0000269|PubMed:7761851,
FT ECO:0000269|PubMed:7819221"
FT MUTAGEN 242
FT /note="K->E: Strongly impairs enzymatic activity."
FT /evidence="ECO:0000269|PubMed:21151122"
FT MUTAGEN 242
FT /note="K->R: Impairs enzymatic activity."
FT /evidence="ECO:0000269|PubMed:21151122"
FT STRAND 15..17
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 25..32
FT /evidence="ECO:0007829|PDB:1PB1"
FT HELIX 38..57
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 58..61
FT /evidence="ECO:0007829|PDB:1IKA"
FT STRAND 64..67
FT /evidence="ECO:0007829|PDB:1PB1"
FT HELIX 72..78
FT /evidence="ECO:0007829|PDB:1PB1"
FT HELIX 86..95
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 96..100
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:1PB1"
FT HELIX 114..121
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 126..132
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:1PB1"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 148..154
FT /evidence="ECO:0007829|PDB:1PB1"
FT HELIX 158..161
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:1IDC"
FT HELIX 170..181
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:1IDC"
FT HELIX 203..219
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 223..229
FT /evidence="ECO:0007829|PDB:1PB1"
FT TURN 231..233
FT /evidence="ECO:0007829|PDB:1PB1"
FT TURN 235..237
FT /evidence="ECO:0007829|PDB:1PB1"
FT HELIX 238..253
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 256..258
FT /evidence="ECO:0007829|PDB:1PB3"
FT STRAND 259..262
FT /evidence="ECO:0007829|PDB:1IKA"
FT STRAND 264..267
FT /evidence="ECO:0007829|PDB:1PB1"
FT TURN 269..271
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 274..281
FT /evidence="ECO:0007829|PDB:1PB1"
FT HELIX 282..291
FT /evidence="ECO:0007829|PDB:1PB1"
FT HELIX 293..295
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 298..301
FT /evidence="ECO:0007829|PDB:1PB1"
FT HELIX 303..316
FT /evidence="ECO:0007829|PDB:1PB1"
FT TURN 320..322
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 333..336
FT /evidence="ECO:0007829|PDB:1PB1"
FT HELIX 343..345
FT /evidence="ECO:0007829|PDB:1PB1"
FT TURN 346..349
FT /evidence="ECO:0007829|PDB:1IDD"
FT HELIX 354..366
FT /evidence="ECO:0007829|PDB:1PB1"
FT HELIX 370..385
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 388..390
FT /evidence="ECO:0007829|PDB:1GRO"
FT HELIX 391..394
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 397..399
FT /evidence="ECO:0007829|PDB:1PB1"
FT STRAND 401..403
FT /evidence="ECO:0007829|PDB:1GRO"
FT HELIX 405..414
FT /evidence="ECO:0007829|PDB:1PB1"
SQ SEQUENCE 416 AA; 45757 MW; 9A02E707C3B4FDD9 CRC64;
MESKVVVPAQ GKKITLQNGK LNVPENPIIP YIEGDGIGVD VTPAMLKVVD AAVEKAYKGE
RKISWMEIYT GEKSTQVYGQ DVWLPAETLD LIREYRVAIK GPLTTPVGGG IRSLNVALRQ
ELDLYICLRP VRYYQGTPSP VKHPELTDMV IFRENSEDIY AGIEWKADSA DAEKVIKFLR
EEMGVKKIRF PEHCGIGIKP CSEEGTKRLV RAAIEYAIAN DRDSVTLVHK GNIMKFTEGA
FKDWGYQLAR EEFGGELIDG GPWLKVKNPN TGKEIVIKDV IADAFLQQIL LRPAEYDVIA
CMNLNGDYIS DALAAQVGGI GIAPGANIGD ECALFEATHG TAPKYAGQDK VNPGSIILSA
EMMLRHMGWT EAADLIVKGM EGAINAKTVT YDFERLMDGA KLLKCSEFGD AIIENM
//
