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discounted EARLY registration ends Dec 31, 2014
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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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MetaCyc Enzyme: isocitrate lyase

Gene: aceA Accession Numbers: EG10022 (MetaCyc), b4015, ECK4007

Synonyms: icl

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of isocitrate lyase = [AceA]4
         isocitrate lyase monomer = AceA

Citations: [Matsuoka88, Rieul88]

Locations: cytosol

Map Position: [4,215,132 -> 4,216,436]

Molecular Weight of Polypeptide: 47.522 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0013128 , CGSC:1052 , DIP:DIP-35893N , EchoBASE:EB0021 , EcoGene:EG10022 , EcoliWiki:b4015 , ModBase:P0A9G6 , OU-Microarray:b4015 , PortEco:aceA , PR:PRO_000022036 , Pride:P0A9G6 , Protein Model Portal:P0A9G6 , RefSeq:NP_418439 , RegulonDB:EG10022 , SMR:P0A9G6 , String:511145.b4015 , UniProt:P0A9G6

Relationship Links: InterPro:IN-FAMILY:IPR000918 , InterPro:IN-FAMILY:IPR006254 , InterPro:IN-FAMILY:IPR015813 , InterPro:IN-FAMILY:IPR018523 , Panther:IN-FAMILY:PTHR21631:SF3 , PDB:Structure:1IGW , Pfam:IN-FAMILY:PF00463 , Prosite:IN-FAMILY:PS00161

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0006097 - glyoxylate cycle Inferred by curator Inferred by computational analysis [UniProtGOA12, UniProtGOA11a, Creaghan78]
GO:0006099 - tricarboxylic acid cycle Inferred by computational analysis [UniProtGOA11a]
GO:0008152 - metabolic process Inferred by computational analysis [GOA01a]
GO:0019752 - carboxylic acid metabolic process Inferred by computational analysis [GOA01a]
Molecular Function: GO:0004451 - isocitrate lyase activity Inferred from experiment Inferred by computational analysis [GOA01, GOA01a, Hoyt88]
GO:0043169 - cation binding Inferred from experiment [Hoyt88]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01a]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment [Lasserre06]
GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11, UniProtGOA11a]

MultiFun Terms: metabolism central intermediary metabolism glyoxylate bypass

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Enzymatic reaction of: isocitrate lyase

EC Number: 4.1.3.1

D-threo-isocitrate <=> glyoxylate + succinate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

This reaction is reversible.

In Pathways: superpathway of glyoxylate bypass and TCA , superpathway of glycolysis, pyruvate dehydrogenase, TCA, and glyoxylate bypass , glyoxylate cycle

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Summary:
The second enzyme of the glyoxylate bypass. In one direction the reaction effects cleavage of isocitrate, in the other direction it effects condensation of glyoxylate and succinate. The enzyme is subject to phosphorylation[Hoyt88, Robertson88]. The enzyme is inactivated by reaction of iodoacetate with a cysteine residue at the active site [Nimmo89]. Values refer to cleavage direction of reaction

Citations: [Ko89]

Cofactors or Prosthetic Groups: Mg2+ [Comment 1]

Alternative Cofactors for Mg2+: Mn2+

Inhibitors (Competitive): phosphoenolpyruvate , 3-phospho-D-glycerate [Comment 2] , malonate [Comment 3] , oxalate [Comment 3]

Inhibitors (Uncompetitive): succinate [Hoyt88, Comment 4] , itaconate [Hoyt88, Comment 5]

Inhibitors (Unknown Mechanism): Hg2+ , 5,5'-dithio-bis-2-nitrobenzoate , 3-nitro-1-propionate [Helmward89, Hoyt88] , 2-hydroxymalonate [Hoyt88, Helmward89] , methylmalonate [Comment 6] , 2-oxoglutarate , phosphoenolpyruvate , Ca2+ , cis-aconitate , chloride , glycolate [Comment 6]

Kinetic Parameters:

Substrate
Km (μM)
Citations
succinate
590.0
[MacKintosh88, BRENDA14]
glyoxylate
130.0
[MacKintosh88, BRENDA14]

pH(opt): 6.9 [BRENDA14, Watanabe04]


Sequence Features

Feature Class Location Citations Comment
Sequence-Conflict 101 -> 117
[Rieul88, UniProt10]
Alternate sequence: WRPACIRISRSIRQTRC; UniProt: (in Ref. 3; CAA30416);
Mutagenesis-Variant 195
[Robertson95a, UniProt11]
Alternate sequence: S; UniProt: Large decrease in activity.
Alternate sequence: A; UniProt: Large decrease in activity.
Active-Site 195
[UniProt10a]
UniProt: Non-Experimental Qualifier: probably;
Sequence-Conflict 215
[Rieul88, UniProt10]
Alternate sequence: P; UniProt: (in Ref. 3; CAA30416);
Sequence-Conflict 293
[Klumpp88, UniProt10]
Alternate sequence: R; UniProt: (in Ref. 8; AAA24009);
Sequence-Conflict 338
[Rieul88, UniProt10]
Alternate sequence: E; UniProt: (in Ref. 3; CAA30416);
Sequence-Conflict 419 -> 434
[Matsuoka88, UniProt10]
Alternate sequence: DVFSHRADRLH; UniProt: (in Ref. 4);

History:
10/20/97 Gene b4015 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10022; confirmed by SwissProt match.


References

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

Creaghan78: Creaghan IT, Guest JR (1978). "Succinate dehydrogenase-dependent nutritional requirement for succinate in mutants of Escherichia coli K12." J Gen Microbiol 107(1);1-13. PMID: 366070

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Helmward89: Helmward Z "Handbook of Enzyme Inhibitors. 2nd, revised and enlarged edition." Weinheim, Federal Republic of Germany ; New York, NY, USA , 1989.

Hoyt88: Hoyt JC, Robertson EF, Berlyn KA, Reeves HC (1988). "Escherichia coli isocitrate lyase: properties and comparisons." Biochim Biophys Acta 1988;966(1);30-5. PMID: 3291954

Klumpp88: Klumpp DJ, Plank DW, Bowdin LJ, Stueland CS, Chung T, LaPorte DC (1988). "Nucleotide sequence of aceK, the gene encoding isocitrate dehydrogenase kinase/phosphatase." J Bacteriol 170(6);2763-9. PMID: 2836370

Ko89: Ko YH, Vanni P, McFadden BA (1989). "The interaction of 3-phosphoglycerate and other substrate analogs with the glyoxylate- and succinate-binding sites of isocitrate lyase." Arch Biochem Biophys 1989;274(1);155-60. PMID: 2673042

Lasserre06: Lasserre JP, Beyne E, Pyndiah S, Lapaillerie D, Claverol S, Bonneu M (2006). "A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis." Electrophoresis 27(16);3306-21. PMID: 16858726

MacKintosh88: MacKintosh C, Nimmo HG (1988). "Purification and regulatory properties of isocitrate lyase from Escherichia coli ML308." Biochem J 1988;250(1);25-31. PMID: 3281659

Matsuoka88: Matsuoka M, McFadden BA (1988). "Isolation, hyperexpression, and sequencing of the aceA gene encoding isocitrate lyase in Escherichia coli." J Bacteriol 1988;170(10);4528-36. PMID: 3049537

Nimmo89: Nimmo HG, Douglas F, Kleanthous C, Campbell DG, MacKintosh C (1989). "Identification of a cysteine residue at the active site of Escherichia coli isocitrate lyase." Biochem J 1989;261(2);431-5. PMID: 2673221

Rieul88: Rieul C, Bleicher F, Duclos B, Cortay JC, Cozzone AJ (1988). "Nucleotide sequence of the aceA gene coding for isocitrate lyase in Escherichia coli." Nucleic Acids Res 1988;16(12);5689. PMID: 3290857

Robertson88: Robertson EF, Hoyt JC, Reeves HC (1988). "Evidence of histidine phosphorylation in isocitrate lyase from Escherichia coli." J Biol Chem 1988;263(5);2477-82. PMID: 3276689

Robertson95a: Robertson AG, Nimmo HG (1995). "Site-directed mutagenesis of cysteine-195 in isocitrate lyase from Escherichia coli ML308." Biochem J 305 ( Pt 1);239-44. PMID: 7826335

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA12: UniProt-GOA (2012). "Gene Ontology annotation based on UniPathway vocabulary mapping."

Watanabe04: Watanabe S, Takada Y (2004). "Amino acid residues involved in cold adaptation of isocitrate lyase from a psychrophilic bacterium, Colwellia maris." Microbiology 150(Pt 10);3393-403. PMID: 15470117


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Mon Dec 22, 2014, biocyc11.