EzCatDB: T00418
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DB codeT00418
RLCP classification1.13.30005.34 : Hydrolysis
3.1144.220195.34 : Transfer
CATH domainDomain 1-.-.-.-
Domain 21.20.-.-
Domain 33.60.20.10 : Glutamine Phosphoribosylpyrophosphate, subunit 1, domain 1Catalytic domain
E.C.2.3.2.2,3.4.19.13


Enzyme Name
UniProtKBKEGG

P18956P54422A9YTT0O25743
Protein nameGamma-glutamyltranspeptidaseGamma-glutamyltranspeptidase

Gamma-glutamyltransferase
   (EC 2.3.2.2)
Glutamyl transpeptidase
   (EC 2.3.2.2)
Alpha-glutamyl transpeptidase
   (EC 2.3.2.2)
Gamma-glutamyl peptidyltransferase
   (EC 2.3.2.2)
Gamma-glutamyl transpeptidase (ambiguous)
   (EC 2.3.2.2)
Gamma-GPT
   (EC 2.3.2.2)
Gamma-GT
   (EC 2.3.2.2)
Gamma-GTP
   (EC 2.3.2.2)
L-gamma-glutamyl transpeptidase
   (EC 2.3.2.2)
L-gamma-glutamyltransferase
   (EC 2.3.2.2)
GGT (ambiguous)
   (EC 3.4.19.13)
Gamma-glutamyltranspeptidase (ambiguous)
   (EC 3.4.19.13)
Glutathione hydrolase
   (EC 3.4.19.13)
Glutathionase
   (EC 3.4.19.13)
SynonymsEC 2.3.2.2
Glutathione hydrolase
EC 3.4.19.13
EC 2.3.2.2
Glutathione hydrolase
EC 3.4.19.13
Gamma glutamyl transpeptidase
EC 2.3.2.2
Gamma-glutamyltranspeptidase
Gamma-glutamyltranspeptidase (Ggt)
ContainsGamma-glutamyltranspeptidase large chain
Gamma-glutamyltranspeptidase small chain
Gamma-glutamyltranspeptidase large chain
Gamma-glutamyltranspeptidase small chain
NoneNone
RefSeqNP_417904.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_491987.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
NP_389723.1 (Protein)
NC_000964.3 (DNA/RNA sequence)

NP_207909.1 (Protein)
NC_000915.1 (DNA/RNA sequence)
YP_006935034.1 (Protein)
NC_018939.1 (DNA/RNA sequence)
MEROPST03.001 (Threonine)
T03.001 (Threonine)
T03.001 (Threonine)
T03.001 (Threonine)
PfamPF01019 (G_glu_transpept)
[Graphical view]
PF01019 (G_glu_transpept)
[Graphical view]
PF01019 (G_glu_transpept)
[Graphical view]
PF01019 (G_glu_transpept)
[Graphical view]

KEGG pathways
MAP codePathwaysE.C.
MAP00430Taurine and hypotaurine metabolism2.3.2.2
MAP00460Cyanoamino acid metabolism2.3.2.2
MAP00480Glutathione metabolism2.3.2.2
MAP00590Arachidonic acid metabolism2.3.2.2

UniProtKB:Accession NumberP18956P54422A9YTT0O25743
Entry nameGGT_ECOLIGGT_BACSUA9YTT0_BACLIO25743_HELPY
ActivityA (5-L-glutamyl)-peptide + an amino acid = a peptide + a 5-L-glutamyl amino acid.Glutathione + H2O = L-cysteinylglycine + L-glutamate.A (5-L-glutamyl)-peptide + an amino acid = a peptide + a 5-L-glutamyl amino acid.Glutathione + H2O = L-cysteinylglycine + L-glutamate.

SubunitThis enzyme consists of two polypeptide chains, which are synthesized in precursor form from a single polypeptide.This enzyme consists of two polypeptide chains, which are synthesized in precursor form from a single polypeptide. By similarity

Subcellular locationPeriplasm.Secreted

Cofactor




Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC03193C00051C00045C00001C00012C01419C03363C00025I00189I00186I00164I00188I00187
E.C.2.3.2.2,3.4.19.132.3.2.2,3.4.19.132.3.2.23.4.19.132.3.2.2,3.4.19.132.3.2.2,3.4.19.132.3.2.23.4.19.132.3.2.2,3.4.19.132.3.2.2,3.4.19.132.3.2.2,3.4.19.132.3.2.23.4.19.13
Compound(5-L-Glutamyl)-peptideGlutathioneAmino acidH2OPeptideCys-Gly5-L-Glutamyl amino acidL-Glutamate(5-L-Glutamyl)-peptide-NterminalThr-enzyme tetrahedral-transition-stateGultathione-NterminalThr-enzyme tetrahedral-transition-stateGamma-glutamyl-NterminalThr-acyl-enzyme intermediateGamma-glutamyl-NterminalThr-AA-enzyme tetrahedral-transition-stateGamma-glutamyl-NterminalThr-enzyme tetrahedral-transition-state
Typeamine group,carboxyl group,peptide/proteinamino acids,carboxyl group,peptide/protein,sulfhydryl groupamino acidsH2Opeptide/proteinamide group,amine group,carboxyl group,sulfhydryl groupamide group,amine group,carboxyl groupamino acids,carboxyl group




ChEBI
16856

15377

4047
61694

16015





PubChem
25246407
124886

962
22247451

7098621
439498

88747398
44272391
33032





                     
2dbuA01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dbuC01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dbwA01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dbwC01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dbxA01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dbxC01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dg5A01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dg5C01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2e0wA01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2e0wB01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2e0xA01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2e0xC01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2e0yA01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2e0yC01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2z8iA01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2z8iC01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2z8jA01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2z8jC01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2z8kA01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2z8kC01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2v36A01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2v36C01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3a75A01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3a75C01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3whqA01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3whrA01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3whsA01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
4ottA01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
4otuA01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2nqoA01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2nqoC01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2qm6A01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2qm6C01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2qmcA01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2qmcC01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3fnmA01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3fnmC01UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dbuA02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dbuC02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dbwA02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dbwC02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dbxA02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dbxC02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dg5A02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dg5C02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2e0wA02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2e0wB02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2e0xA02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2e0xC02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2e0yA02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2e0yC02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2z8iA02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2z8iC02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2z8jA02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2z8jC02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2z8kA02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2z8kC02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2v36A02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2v36C02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3a75A02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3a75C02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3whqA02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3whrA02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3whsA02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
4ottA02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
4otuA02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2nqoA02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2nqoC02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2qm6A02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2qm6C02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2qmcA02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2qmcC02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3fnmA02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3fnmC02UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dbuB00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dbuD00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dbwB00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundIntermediate-bound:GGLUnboundUnbound
2dbwD00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundIntermediate-bound:GGLUnboundUnbound
2dbxB00UnboundUnboundUnbound UnboundUnboundUnboundBound:GLUUnboundUnboundUnboundUnboundUnbound
2dbxD00UnboundUnboundUnbound UnboundUnboundUnboundBound:GLUUnboundUnboundUnboundUnboundUnbound
2dg5B00UnboundUnboundUnbound UnboundUnboundUnboundBound:GLUUnboundUnboundUnboundUnboundUnbound
2dg5D00UnboundUnboundUnbound UnboundUnboundUnboundBound:GLUUnboundUnboundUnboundUnboundUnbound
2e0xB00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2e0xD00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2e0yB00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2e0yD00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2z8iB00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundTransition-state-analogue:AZS
2z8iD00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundTransition-state-analogue:AZS
2z8jB00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundTransition-state-analogue:AZSUnbound
2z8jD00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundTransition-state-analogue:AZSUnbound
2z8kB00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundIntermediate-analogue:AVNUnboundUnbound
2z8kD00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundIntermediate-analogue:AVNUnboundUnbound
2v36B00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2v36D00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3a75B00UnboundUnboundUnbound UnboundUnboundUnboundBound:GLUUnboundUnboundUnboundUnboundUnbound
3a75D00UnboundUnboundUnbound UnboundUnboundUnboundBound:GLUUnboundUnboundUnboundUnboundUnbound
3whqB00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3whrB00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3whsB00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundIntermediate-analogue:AVNUnboundUnbound
4ottB00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
4otuB00UnboundUnboundUnbound UnboundUnboundUnboundBound:GLUUnboundUnboundUnboundUnboundUnbound
2nqoB00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2nqoD00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2qm6B00UnboundUnboundUnbound UnboundUnboundUnboundBound:GLUUnboundUnboundUnboundUnboundUnbound
2qm6D00UnboundUnboundUnbound UnboundUnboundUnboundBound:GLUUnboundUnboundUnboundUnboundUnbound
2qmcB00UnboundAnalogue:GTBUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2qmcD00UnboundAnalogue:GTBUnbound UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3fnmB00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundIntermediate-analogue:AVNUnboundUnbound
3fnmD00UnboundUnboundUnbound UnboundUnboundUnboundUnboundUnboundUnboundIntermediate-analogue:AVNUnboundUnbound

Active-site residues
resource
literature[9],[10],[19]
pdbCatalytic residuesMain-chain involved in catalysiscomment
           
2dbuA01       
 
 
2dbuC01       
 
 
2dbwA01       
 
 
2dbwC01       
 
 
2dbxA01       
 
 
2dbxC01       
 
 
2dg5A01       
 
 
2dg5C01       
 
 
2e0wA01       
GLY 483;GLY 484
proenzyme
2e0wB01       
GLY 483;GLY 484
proenzyme
2e0xA01       
 
 
2e0xC01       
 
 
2e0yA01       
 
 
2e0yC01       
 
 
2z8iA01       
 
 
2z8iC01       
 
 
2z8jA01       
 
 
2z8jC01       
 
 
2z8kA01       
 
 
2z8kC01       
 
 
2v36A01       
 
 
2v36C01       
 
 
3a75A01       
 
 
3a75C01       
 
 
3whqA01       
 
 
3whrA01       
 
 
3whsA01       
 
 
4ottA01       
 
 
4otuA01       
 
 
2nqoA01       
 
 
2nqoC01       
 
 
2qm6A01       
 
 
2qm6C01       
 
 
2qmcA01       
 
 
2qmcC01       
 
 
3fnmA01       
 
 
3fnmC01       
 
 
2dbuA02       
 
 
2dbuC02       
 
 
2dbwA02       
 
 
2dbwC02       
 
 
2dbxA02       
 
 
2dbxC02       
 
 
2dg5A02       
 
 
2dg5C02       
 
 
2e0wA02       ;THR 409
       ;THR 409
proenzyme, mutant T391A
2e0wB02       ;THR 409
       ;THR 409
proenzyme, mutant T391A
2e0xA02       
 
 
2e0xC02       
 
 
2e0yA02       
 
 
2e0yC02       
 
 
2z8iA02       
 
 
2z8iC02       
 
 
2z8jA02       
 
 
2z8jC02       
 
 
2z8kA02       
 
 
2z8kC02       
 
 
2v36A02       
 
 
2v36C02       
 
 
3a75A02       
 
 
3a75C02       
 
 
3whqA02       
 
 
3whrA02       
 
 
3whsA02       
 
 
4ottA02       
 
 
4otuA02       
 
 
2nqoA02       
 
 
2nqoC02       
 
 
2qm6A02       
 
 
2qm6C02       
 
 
2qmcA02       
 
 
2qmcC02       
 
 
3fnmA02       
 
 
3fnmC02       
 
 
2dbuB00THR 391;THR 409
THR 391;GLY 483;GLY 484
 
2dbuD00THR 391;THR 409
THR 391;GLY 483;GLY 484
 
2dbwB00THR 391;THR 409
THR 391;GLY 483;GLY 484
 
2dbwD00THR 391;THR 409
THR 391;GLY 483;GLY 484
 
2dbxB00THR 391;THR 409
THR 391;GLY 483;GLY 484
 
2dbxD00THR 391;THR 409
THR 391;GLY 483;GLY 484
 
2dg5B00THR 391;THR 409
THR 391;GLY 483;GLY 484
 
2dg5D00THR 391;THR 409
THR 391;GLY 483;GLY 484
 
2e0xB00THR 391;THR 409
THR 391;GLY 483;GLY 484
 
2e0xD00THR 391;THR 409
THR 391;GLY 483;GLY 484
 
2e0yB00THR 391;THR 409
THR 391;GLY 483;GLY 484
 
2e0yD00THR 391;THR 409
THR 391;GLY 483;GLY 484
 
2z8iB00THR 391;THR 409
THR 391;GLY 483;GLY 484
 
2z8iD00THR 391;THR 409
THR 391;GLY 483;GLY 484
 
2z8jB00THR 391;THR 409
THR 391;GLY 483;GLY 484
 
2z8jD00THR 391;THR 409
THR 391;GLY 483;GLY 484
 
2z8kB00THR 391;THR 409
THR 391;GLY 483;GLY 484
 
2z8kD00THR 391;THR 409
THR 391;GLY 483;GLY 484
 
2v36B00THR 403;THR 421
THR 403;GLY 485;GLY 486
 
2v36D00THR 403;THR 421
THR 403;GLY 485;GLY 486
 
3a75B00THR 403;THR 421
THR 403;GLY 485;GLY 486
 
3a75D00THR 403;THR 421
THR 403;GLY 485;GLY 486
 
3whqB00THR 403;THR 421
THR 403;GLY 485;GLY 486
 
3whrB00THR 403;THR 421
THR 403;GLY 485;GLY 486
 
3whsB00THR 403;THR 421
THR 403;GLY 485;GLY 486
 
4ottB00THR 399;THR 417
THR 399;GLY 481;GLY 482
 
4otuB00THR 399;THR 417
THR 399;GLY 481;GLY 482
 
2nqoB00THR 380;THR 398
THR 380;GLY 472;GLY 473
 
2nqoD00THR 380;THR 398
THR 380;GLY 472;GLY 473
 
2qm6B00THR 380;THR 398
THR 380;GLY 472;GLY 473
 
2qm6D00THR 380;THR 398
THR 380;GLY 472;GLY 473
 
2qmcB00       ;THR 398
       ;GLY 472;GLY 473
mutant T380A
2qmcD00       ;THR 398
       ;GLY 472;GLY 473
mutant T380A
3fnmB00THR 380;THR 398
THR 380;GLY 472;GLY 473
 
3fnmD00THR 380;THR 398
THR 380;GLY 472;GLY 473
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[10]p.6473-6474
[12]Fig.6, p.540

references
[1]
PubMed ID7903400
JournalJ Mol Biol
Year1993
Volume234
Pages1259-62
AuthorsKumagai H, Nohara S, Suzuki H, Hashimoto W, Yamamoto K, Sakai H, Sakabe K, Fukuyama K, Sakabe N
TitleCrystallization and preliminary X-ray analysis of gamma-glutamyltranspeptidase from Escherichia coli K-12.
[2]
PubMed ID7818493
JournalBiochem J
Year1994
Volume304
Pages869-76
AuthorsGololobov MYu, Bateman RC Jr
Titlegamma-Glutamyltranspeptidase-catalysed acyl-transfer to the added acceptor does not proceed via the ping-pong mechanism.
[3]
PubMed ID8864839
JournalJ Biochem
Year1996
Volume120
Pages26-8
AuthorsSakai H, Sakabe N, Sasaki K, Hashimoto W, Suzuki H, Tachi H, Kumagai H, Sakabe K
TitleA preliminary description of the crystal structure of gamma-glutamyltranspeptidase from E. coli K-12.
[4]
PubMed ID12207027
JournalJ Biol Chem
Year2002
Volume277
Pages43536-43
AuthorsSuzuki H, Kumagai H
TitleAutocatalytic processing of gamma-glutamyltranspeptidase.
[5]
PubMed ID14516202
JournalBiochemistry
Year2003
Volume42
Pages11504-13
AuthorsCastonguay R, Lherbet C, Keillor JW
TitleKinetic studies of rat kidney gamma-glutamyltranspeptidase deacylation reveal a general base-catalyzed mechanism.
[6]
PubMed ID12643897
JournalBioorg Med Chem Lett
Year2003
Volume13
Pages997-1000
AuthorsLherbet C, Morin M, Castonguay R, Keillor JW
TitleSynthesis of aza and oxaglutamyl-p-nitroanilide derivatives and their kinetic studies with gamma-glutamyltranspeptidase.
[7]
PubMed ID15466585
JournalAppl Environ Microbiol
Year2004
Volume70
Pages6324-8
AuthorsSuzuki H, Miwa C, Ishihara S, Kumagai H
TitleA single amino acid substitution converts gamma-glutamyltranspeptidase to a class IV cephalosporin acylase (glutaryl-7-aminocephalosporanic acid acylase).
[8]
PubMed ID16399402
JournalMethods Enzymol
Year2005
Volume401
Pages449-67
AuthorsKeillor JW, Castonguay R, Lherbet C
TitleGamma-glutamyl transpeptidase substrate specificity and catalytic mechanism.
[9]
PubMed ID16672227
JournalJ Biol Chem
Year2006
Volume281
Pages19029-37
AuthorsBoanca G, Sand A, Barycki JJ
TitleUncoupling the enzymatic and autoprocessing activities of Helicobacter pylori gamma-glutamyltranspeptidase.
[10]
PubMed ID16618936
JournalProc Natl Acad Sci U S A
Year2006
Volume103
Pages6471-6
AuthorsOkada T, Suzuki H, Wada K, Kumagai H, Fukuyama K
TitleCrystal structures of gamma-glutamyltranspeptidase from Escherichia coli, a key enzyme in glutathione metabolism, and its reaction intermediate.
Related PDB2dbu,2dbw,2dbx,2dg5
[11]
PubMed ID17960917
JournalBiochemistry
Year2007
Volume46
Pages13407-14
AuthorsMorrow AL, Williams K, Sand A, Boanca G, Barycki JJ
TitleCharacterization of Helicobacter pylori gamma-glutamyltranspeptidase reveals the molecular basis for substrate specificity and a critical role for the tyrosine 433-containing loop in catalysis.
Related PDB2qm6,2qmc
[12]
PubMed ID17107958
JournalJ Biol Chem
Year2007
Volume282
Pages534-41
AuthorsBoanca G, Sand A, Okada T, Suzuki H, Kumagai H, Fukuyama K, Barycki JJ
TitleAutoprocessing of Helicobacter pylori gamma-glutamyltranspeptidase leads to the formation of a threonine-threonine catalytic dyad.
Related PDB2nqo
[13]
PubMed ID17135273
JournalJ Biol Chem
Year2007
Volume282
Pages2433-9
AuthorsOkada T, Suzuki H, Wada K, Kumagai H, Fukuyama K
TitleCrystal structure of the gamma-glutamyltranspeptidase precursor protein from Escherichia coli. Structural changes upon autocatalytic processing and implications for the maturation mechanism.
Related PDB2e0w,2e0x,2e0y
[14]
PubMed ID18036555
JournalBiochem Biophys Res Commun
Year2008
Volume366
Pages294-300
AuthorsOng PL, Yao YF, Weng YM, Hsu WH, Lin LL
TitleResidues Arg114 and Arg337 are critical for the proper function of Escherichia coli gamma-glutamyltranspeptidase.
[15]
PubMed ID18555071
JournalJ Mol Biol
Year2008
Volume380
Pages361-72
AuthorsWada K, Hiratake J, Irie M, Okada T, Yamada C, Kumagai H, Suzuki H, Fukuyama K
TitleCrystal structures of Escherichia coli gamma-glutamyltranspeptidase in complex with azaserine and acivicin: novel mechanistic implication for inhibition by glutamine antagonists.
Related PDB2z8i,2z8j,2z8k
[16]
PubMed ID19256527
JournalBiochemistry
Year2009
Volume48
Pages2459-67
AuthorsWilliams K, Cullati S, Sand A, Biterova EI, Barycki JJ
TitleCrystal structure of acivicin-inhibited gamma-glutamyltranspeptidase reveals critical roles for its C-terminus in autoprocessing and catalysis.
Related PDB3fnm
[17]
PubMed ID19788059
JournalIndian J Biochem Biophys
Year2009
Volume46
Pages281-8
AuthorsHsu WH, Ong PL, Chen SC, Lin LL
TitleContribution of Ser463 residue to the enzymatic and autoprocessing activities of Escherichia coli gamma-glutamyltranspeptidase.
[18]
PubMed ID20572278
JournalBiotechnol J
Year2010
Volume5
Pages829-37
AuthorsSuzuki H, Yamada C, Kijima K, Ishihara S, Wada K, Fukuyama K, Kumagai H
TitleEnhancement of glutaryl-7-aminocephalosporanic acid acylase activity of gamma-glutamyltranspeptidase of Bacillus subtilis.
[19]
PubMed ID20088880
JournalFEBS J
Year2010
Volume277
Pages1000-9
AuthorsWada K, Irie M, Suzuki H, Fukuyama K
TitleCrystal structure of the halotolerant gamma-glutamyltranspeptidase from Bacillus subtilis in complex with glutamate reveals a unique architecture of the solvent-exposed catalytic pocket.
Related PDB3a75
[20]
PubMed ID21298394
JournalExtremophiles
Year2011
Volume15
Pages259-70
AuthorsCastellano I, Di Salle A, Merlino A, Rossi M, La Cara F
TitleGene cloning and protein expression of ƒÁ-glutamyltranspeptidases from Thermus thermophilus and Deinococcus radiodurans: comparison of molecular and structural properties with mesophilic counterparts.
[21]
PubMed ID22664192
JournalEnzyme Microb Technol
Year2012
Volume51
Pages86-94
AuthorsHu HY, Yang JC, Chen JH, Chi MC, Lin LL
TitleEnzymatic characterization of Bacillus licheniformis ƒÁ-glutamyltranspeptidase fused with N-terminally truncated forms of Bacillus sp. TS-23 ƒ¿-amylase.
[22]
PubMed ID23036908
JournalBiochim Biophys Acta
Year2013
Volume1834
Pages149-57
AuthorsPica A, Russo Krauss I, Castellano I, La Cara F, Graziano G, Sica F, Merlino A
TitleEffect of NaCl on the conformational stability of the thermophilic ƒÁ-glutamyltranspeptidase from Geobacillus thermodenitrificans: Implication for globular protein halotolerance.
[23]
PubMed ID24531494
JournalActa Crystallogr D Biol Crystallogr
Year2014
Volume70
Pages607-14
AuthorsIda T, Suzuki H, Fukuyama K, Hiratake J, Wada K
TitleStructure of Bacillus subtilis gamma-glutamyltranspeptidase in complex with acivicin: diversity of the binding mode of a classical and electrophilic active-site-directed glutamate analogue.
Related PDB3whq,3whr,3whs
[24]
PubMed ID24780583
JournalBiochim Biophys Acta
Year2014
Volume1844
Pages1523-9
AuthorsLin LL, Chen YY, Chi MC, Merlino A
TitleLow resolution X-ray structure of gamma-glutamyltranspeptidase from Bacillus licheniformis: opened active site cleft and a cluster of acid residues potentially involved in the recognition of a metal ion.
Related PDB4ott,4otu

comments
This enzyme belongs to the N-terminal nucleophile (Ntn) hydrolase superfamily (CATH 3.60.20.10) (see [4], [9]). This enzyme consists of one large subunit and one small subunit, which are generated from an inactive precursor protein through an intramolecular autocatalytic processing (or autoprocessing) ([4], [9]).
The oxygen atom of the sidechain of the N-terminal residue of the small subunit, threonine, acts as a nucleophile in both the autocatalytic processing and enzymatic reactions ([4], [9]). This residue is invariably conserved throughout all the homologous enzymes.
As for a general base, alpha-amino group of the newly generated N-terminal residue on processing acts in the enzymatic reactions in the Ntn hydrolase superfamily, whereas it has not been elucidated for the autoctalytic processing reaction of this enzyme (see [4]).
This enzyme catalyzes the hydrolysis of gamma-glutamyl bonds in gamma-glutamyl compounds such as glutathione (EC 3.4.19.13) and the transfer of the gamma-glutamyl group to other amino acids and short peptides (EC 2.3.2.2) (see [3], [5], [8], [9], [10]).
According to the literature ([11], [12]), this enzyme catalyzes the hydrolysis reaction as follows:
(h1) The N-terminal alpha-amino group of Thr380 (of 2nqo, 2qm6) on the small subunit acts as a general base to enhance the nucleophilicity of the sidechain of Thr380, whereas the sidechain hydroxyl group of Thr398 may modulate the activity of sidechain and the alpha-amino group of Thr380. (Thr398 modulate the alpha-amino group of Thr380 throughout the reaction.)
(h2) The activated Thr380 makes a nucleophilic attack on the gamma-glutamyl peptide bond of glutathione, leading to formation of the tetrahedral intermediate (I00186).
(h3) The tetrahedral intermediate (I00186) is stabilized by the oxyanion hole composed of the mainchain amide groups of Gly472 and Gly473.
(h4) The alpha-amino group of Thr380 acts as a general acid to protonate the leaving group, Cys-Gly portion of the intermedaite (I00186), to facilitate the collapse of the intermediate. This reaction leads to the formation of an acyl enzyme intermediate (I00164). This intermediate is stabilized by the amide group of Gly472.
(h5) The alpha-amino group of Thr380 acts as a general base to activate a incoming water molecule.
(h6) The activated water makes a nucleophilic attack on the acyl enzyme intermediate (I00164), forming the tetrahedral intermediate (I00187). This intermediate is also stabilized by the oxyanion hole (Gly472 and Gly473).
(h7) The alpha-amino group of Thr380 may act as a general acid to protonate its own sidechain, facilitating the release of gamma-glutamyl group as a leaving Glu. By this, the active site is regenerated.
Similarly, this enzyme catalyzes the transfer reaction as follows:
(t1) The N-terminal alpha-amino group of Thr380 (of 2nqo, 2qm6) on the small subunit acts as a general base to enhance the nucleophilicity of the sidechain of Thr380, whereas the sidechain hydroxyl group of Thr398 may modulate the activity of sidechain and the alpha-amino group of Thr380. (Thr398 modulate the alpha-amino group of Thr380 throughout the reaction.)
(t2) The activated Thr380 makes a nucleophilic attack on the gamma-glutamyl peptide bond of glutathione, leading to formation of the tetrahedral intermediate (I00186).
(t3) The tetrahedral intermediate (I00186) is stabilized by the oxyanion hole composed of the mainchain amide groups of Gly472 and Gly473.
(t4) The alpha-amino group of Thr380 acts as a general acid to protonate the leaving group, Cys-Gly portion of the intermedaite (I00186), to facilitate the collapse of the intermediate. This reaction leads to the formation of an acyl enzyme intermediate (I00164). This intermediate is stabilized by the amide group of Gly472.
(t5) The alpha-amino group of Thr380 acts as a general base to activate the amino group of a incoming amino acid.
(t6) The activated amino group of the amino acid makes a nucleophilic attack on the acyl enzyme intermediate (I00164), forming the tetrahedral intermediate (I00188). This intermediate is also stabilized by the oxyanion hole (Gly472 and Gly473).
(t7) The alpha-amino group of Thr380 may act as a general acid to protonate its own sidechain, facilitating the release of L-glutamyl amino acid as a leaving group. By this, the active site is regenerated.
During the autoprocessing, the reaction proceeds similarly to the hydrolysis and transfer reactions, except that the alpha-amino group of Thr380 is not available (see [13]). Instead of the alpha-amino group of Thr380 in the mature enzyme, a water molecule may act as a general base to activate the nucleophile, Thr, in the autoprocessing (see [13]).

createdupdated
2013-08-102015-10-27
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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