MetaCyc Enzyme: glutamate decarboxylase A

Gene: gadA Accession Numbers: EG50009 (MetaCyc), b3517, ECK3502

Synonyms: gadS

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of glutamate decarboxylase A = [GadA]6
         glutamate decarboxylase A subunit = GadA

GadA, a glutamate decarboxylase enzyme, is part of the glutamate-dependent acid resistance system 2 (AR2) which confers resistance to extreme acid conditions. There are two distinct E. coli GAD polypeptides which are highly similar to one another. AR2 also protects the cell during anaerobic phosphate starvation when glutamate is available by preventing damage from weak acids produced from carbohydrate fermentation. gadABC mutants have reduced viability after anaerobic phosphate starvation compared to wild-type [Moreau07].

The crystal structure of the hexameric GadA in complex with the substrate analog glutarate has been determined to a resolution of 2.05 Å [Dutyshev05].

Regulation has been described [Ma03].

Citations: [Smith92, Lin95a, De99]

Locations: membrane, cytosol

Map Position: [3,664,203 <- 3,665,603]

Molecular Weight of Polypeptide: 52.685 kD (from nucleotide sequence)

pI [VanBogelen92]: 5.54, 5.62

Unification Links: ASAP:ABE-0011490 , CGSC:32191 , DIP:DIP-36201N , EchoBASE:EB4302 , EcoGene:EG50009 , EcoliWiki:b3517 , Mint:MINT-1224142 , ModBase:P69908 , OU-Microarray:b3517 , PortEco:gadA , PR:PRO_000022741 , Pride:P69908 , Protein Model Portal:P69908 , RefSeq:NP_417974 , RegulonDB:EG50009 , SMR:P69908 , String:511145.b3517 , UniProt:P69908

Relationship Links: InterPro:IN-FAMILY:IPR002129 , InterPro:IN-FAMILY:IPR010107 , InterPro:IN-FAMILY:IPR015421 , InterPro:IN-FAMILY:IPR015424 , InterPro:IN-FAMILY:IPR021115 , Panther:IN-FAMILY:PTHR11999:SF1 , PDB:Structure:1XEY , Pfam:IN-FAMILY:PF00282 , Prosite:IN-FAMILY:PS00392

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

GO Terms:

Biological Process: GO:0051454 - intracellular pH elevation Inferred from experiment [CastanieCornet99]
GO:0006536 - glutamate metabolic process Inferred by computational analysis [GOA01a]
GO:0019752 - carboxylic acid metabolic process Inferred by computational analysis [GOA01a]
Molecular Function: GO:0004351 - glutamate decarboxylase activity Inferred from experiment Inferred by computational analysis [GOA01, GOA01a, De96]
GO:0005515 - protein binding Inferred from experiment [Zheng11]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01a]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11a]
GO:0016831 - carboxy-lyase activity Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0030170 - pyridoxal phosphate binding Inferred by computational analysis [GOA01a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment [Lasserre06]
GO:0016020 - membrane Inferred from experiment [Lasserre06]

MultiFun Terms: cell processes adaptations pH

Imported from EcoCyc 02-Jun-2015 by Paley S , SRI International

Enzymatic reaction of: glutamate decarboxylase A

Synonyms: GAD α, glutamate decarboxylase α, L-glutamate 1-carboxy-lyase

EC Number:

L-glutamate + H+ <=> CO2 + 4-aminobutanoate

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

The reaction is irreversible in the direction shown.

In Pathways: glutamate dependent acid resistance

Imported from EcoCyc 02-Jun-2015 by Paley S , SRI International

There are two isozymes for glutamate decarboxylase in E. coli encoded by the gadA and gadB genes. When cells are grown at pH 2.5 with glutamate, the internal pH reaches 4.2 which reflects the pH optimum of the glutamate decarboxylases [Richard04a]. The isozymes have identical functional properties and their amino acid sequences differ in only five residues. Their level of expression seems to be the only significant difference between them. The enzyme is also capable of catalyzing the cleavage of α-methylglutamate into ammonia and laevulinc acid [De96, Bertoldi99].

Many aliphatic mono-, di- and tricarboxylic acids are competitive inhibitors. [Fonda85, Gerig79]

Cofactors or Prosthetic Groups: pyridoxal 5'-phosphate [Comment 1]

Activators (Unknown Mechanism): F [Fonda85] , Br [Fonda85] , Cl [Fonda85]

Inhibitors (Competitive): 3,5-dihydroxybenzoate [Youngs91, Helmward89] , protocatechuate [Youngs91, Helmward89] , chelidonate [Youngs91, Helmward89] , chelidamate [Youngs91, Helmward89] , 3-mercaptopropanoate [Youngs91, Helmward89] , 4-bromoisophthalate [Youngs91, Helmward89] , terephthalate [Fonda72] , isophthalate [Youngs91, Fonda72] , glutaconate [Fonda72] , azelate [Fonda72] , suberate [Fonda72] , glutarate [Fonda72, Helmward89] , 4,5-dihydroxyisophthalate [Youngs91, Helmward89] , 2-mercaptosuccinate [Youngs91, Helmward89] , adipate [Fonda72, Helmward89] , pimelate [Fonda72, Helmward89] , oxalate [Fonda72] , malonate [Fonda72] , succinate [Fonda72] , maleate [Fonda72] , fumarate [Fonda72] , acetylenedicarboxylate [Fonda72] , phthalate [Fonda72] , gallate [Youngs91, Helmward89]

Inhibitors (Unknown Mechanism): cyclogutamate [Helmward89] , Zn2+ [Helmward89] , Hg2+ [Helmward89] , Cu2+ [Helmward89] , Cd2+ [Helmward89]

Kinetic Parameters:

Km (μM)
kcat (sec-1)
kcat/Km (sec-1 μM-1)
[Fonda85, BRENDA14]
[Pennacchietti09, BRENDA14]

pH(opt): 3.8 [BRENDA14, Pennacchietti09], 4 [BRENDA14, McCormick01]

Sequence Features

Feature Class Location Citations Comment
Amino-Acid-Sites-That-Bind 62
UniProt: Substrate; Non-Experimental Qualifier: by similarity;
Sequence-Conflict 64
[Maras92, UniProt10a]
UniProt: (in Ref. 2; AA sequence);
Sequence-Conflict 73
[Maras92, UniProt10a]
UniProt: (in Ref. 2; AA sequence);
Amino-Acid-Sites-That-Bind 83
UniProt: Substrate; Non-Experimental Qualifier: by similarity;
Protein-Segment 126 -> 127
UniProt: Pyridoxal phosphate binding; Sequence Annotation Type: region of interest; Non-Experimental Qualifier: by similarity;
Sequence-Conflict 153
[Maras92, UniProt10a]
UniProt: (in Ref. 2; AA sequence);
Sequence-Conflict 165
[Maras92, UniProt10a]
UniProt: (in Ref. 2; CAA44834);
Sequence-Conflict 208
[Maras92, UniProt10a]
UniProt: (in Ref. 2; CAA44834);
Amino-Acid-Sites-That-Bind 212
UniProt: Pyridoxal phosphate; Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 275
UniProt: Pyridoxal phosphate; Non-Experimental Qualifier: by similarity;
N6-pyridoxal-phosphate-Lys-Modification 276
UniProt: N6-(pyridoxal phosphate)lysine.
Sequence-Conflict 295
[Maras92, UniProt10a]
UniProt: (in Ref. 2; CAA44834);
Sequence-Conflict 355
[Maras92, UniProt10a]
UniProt: (in Ref. 2; AA sequence);

10/20/97 Gene b3517 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG50009; confirmed by SwissProt match.


Bertoldi99: Bertoldi M, Carbone V, Borri Voltattorni C (1999). "Ornithine and glutamate decarboxylases catalyse an oxidative deamination of their alpha-methyl substrates." Biochem J 1999;342 Pt 3;509-12. PMID: 10477260

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014."

CastanieCornet99: Castanie-Cornet MP, Penfound TA, Smith D, Elliott JF, Foster JW (1999). "Control of acid resistance in Escherichia coli." J Bacteriol 181(11);3525-35. PMID: 10348866

De96: De Biase D, Tramonti A, John RA, Bossa F (1996). "Isolation, overexpression, and biochemical characterization of the two isoforms of glutamic acid decarboxylase from Escherichia coli." Protein Expr Purif 1996;8(4);430-8. PMID: 8954890

De99: De Biase D, Tramonti A, Bossa F, Visca P (1999). "The response to stationary-phase stress conditions in Escherichia coli: role and regulation of the glutamic acid decarboxylase system." Mol Microbiol 32(6);1198-211. PMID: 10383761

Dutyshev05: Dutyshev DI, Darii EL, Fomenkova NP, Pechik IV, Polyakov KM, Nikonov SV, Andreeva NS, Sukhareva BS (2005). "Structure of Escherichia coli glutamate decarboxylase (GADalpha) in complex with glutarate at 2.05 angstroms resolution." Acta Crystallogr D Biol Crystallogr 61(Pt 3);230-5. PMID: 15735332

Fonda72: Fonda ML (1972). "Glutamate decarboxylase. Substrate specificity and inhibition by carboxylic acids." Biochemistry 1972;11(7);1304-9. PMID: 4552052

Fonda85: Fonda ML (1985). "L-Glutamate decarboxylase from bacteria." Methods Enzymol 1985;113;11-6. PMID: 3910996

Gerig79: Gerig JT, Kwock L (1979). "Inhibition of bacterial glutamate decarboxylase by tricarboxylic acid cycle intermediates." FEBS Lett 1979;105(1);155-7. PMID: 385341

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.

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

Lin95a: Lin J, Lee IS, Frey J, Slonczewski JL, Foster JW (1995). "Comparative analysis of extreme acid survival in Salmonella typhimurium, Shigella flexneri, and Escherichia coli." J Bacteriol 177(14);4097-104. PMID: 7608084

Ma03: Ma Z, Gong S, Richard H, Tucker DL, Conway T, Foster JW (2003). "GadE (YhiE) activates glutamate decarboxylase-dependent acid resistance in Escherichia coli K-12." Mol Microbiol 49(5);1309-20. PMID: 12940989

Maras92: Maras B, Sweeney G, Barra D, Bossa F, John RA (1992). "The amino acid sequence of glutamate decarboxylase from Escherichia coli. Evolutionary relationship between mammalian and bacterial enzymes." Eur J Biochem 204(1);93-8. PMID: 1740158

McCormick01: McCormick SJ, Tunnicliff G (2001). "Kinetics of inactivation of glutamate decarboxylase by cysteine-specific reagents." Acta Biochim Pol 48(2);573-8. PMID: 11732626

Moreau07: Moreau PL (2007). "The lysine decarboxylase CadA protects Escherichia coli starved of phosphate against fermentation acids." J Bacteriol 189(6);2249-61. PMID: 17209032

Pennacchietti09: Pennacchietti E, Lammens TM, Capitani G, Franssen MC, John RA, Bossa F, De Biase D (2009). "Mutation of His465 alters the pH-dependent spectroscopic properties of Escherichia coli glutamate decarboxylase and broadens the range of its activity toward more alkaline pH." J Biol Chem 284(46);31587-96. PMID: 19797049

Richard04a: Richard H, Foster JW (2004). "Escherichia coli glutamate- and arginine-dependent acid resistance systems increase internal pH and reverse transmembrane potential." J Bacteriol 186(18);6032-41. PMID: 15342572

Smith92: Smith DK, Kassam T, Singh B, Elliott JF (1992). "Escherichia coli has two homologous glutamate decarboxylase genes that map to distinct loci." J Bacteriol 1992;174(18);5820-6. PMID: 1522060

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt15: UniProt Consortium (2015). "UniProt version 2015-01 released on 2015-01-16 00:00:00." Database.

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

VanBogelen92: VanBogelen RA, Sankar P, Clark RL, Bogan JA, Neidhardt FC (1992). "The gene-protein database of Escherichia coli: edition 5." Electrophoresis 1992;13(12);1014-54. PMID: 1286664

Youngs91: Youngs TL, Tunnicliff G (1991). "Substrate analogues and divalent cations as inhibitors of glutamate decarboxylase from Escherichia coli." Biochem Int 1991;23(5);915-22. PMID: 1883399

Zheng11: Zheng C, Yang L, Hoopmann MR, Eng JK, Tang X, Weisbrod CR, Bruce JE (2011). "Cross-linking measurements of in vivo protein complex topologies." Mol Cell Proteomics 10(10);M110.006841. PMID: 21697552

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 19.0 on Mon Aug 3, 2015, BIOCYC14B.