DB code: T00418

RLCP classification 1.13.30005.34 : Hydrolysis
3.1144.220195.34 : Transfer
CATH domain -.-.-.- :
1.20.-.- :
3.60.20.10 : Glutamine Phosphoribosylpyrophosphate, subunit 1, domain 1 Catalytic domain
E.C. 2.3.2.2 3.4.19.13
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq MEROPS Pfam
P18956 Gamma-glutamyltranspeptidase
EC 2.3.2.2
Glutathione hydrolase
EC 3.4.19.13
Gamma-glutamyltranspeptidase large chain
Gamma-glutamyltranspeptidase small chain
NP_417904.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_491987.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
T03.001 (Threonine)
PF01019 (G_glu_transpept)
[Graphical View]
P54422 Gamma-glutamyltranspeptidase
EC 2.3.2.2
Glutathione hydrolase
EC 3.4.19.13
Gamma-glutamyltranspeptidase large chain
Gamma-glutamyltranspeptidase small chain
NP_389723.1 (Protein)
NC_000964.3 (DNA/RNA sequence)
T03.001 (Threonine)
PF01019 (G_glu_transpept)
[Graphical View]
A9YTT0
Gamma glutamyl transpeptidase
EC 2.3.2.2
None T03.001 (Threonine)
PF01019 (G_glu_transpept)
[Graphical View]
O25743
Gamma-glutamyltranspeptidase
Gamma-glutamyltranspeptidase (Ggt)
None NP_207909.1 (Protein)
NC_000915.1 (DNA/RNA sequence)
YP_006935034.1 (Protein)
NC_018939.1 (DNA/RNA sequence)
T03.001 (Threonine)
PF01019 (G_glu_transpept)
[Graphical View]

KEGG enzyme name
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 )

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P18956 GGT_ECOLI A (5-L-glutamyl)-peptide + an amino acid = a peptide + a 5-L-glutamyl amino acid.Glutathione + H2O = L-cysteinylglycine + L-glutamate. This enzyme consists of two polypeptide chains, which are synthesized in precursor form from a single polypeptide. Periplasm.
P54422 GGT_BACSU A (5-L-glutamyl)-peptide + an amino acid = a peptide + a 5-L-glutamyl amino acid.Glutathione + H2O = L-cysteinylglycine + L-glutamate. This enzyme consists of two polypeptide chains, which are synthesized in precursor form from a single polypeptide. By similarity Secreted
A9YTT0 A9YTT0_BACLI
O25743 O25743_HELPY

KEGG Pathways
Map code Pathways E.C.
MAP00430 Taurine and hypotaurine metabolism 2.3.2.2
MAP00460 Cyanoamino acid metabolism 2.3.2.2
MAP00480 Glutathione metabolism 2.3.2.2
MAP00590 Arachidonic acid metabolism 2.3.2.2

Compound table
Substrates Products Intermediates
KEGG-id C03193 C00051 C00045 C00001 C00012 C01419 C03363 C00025 I00189 I00186 I00164 I00188 I00187
E.C. 2.3.2.2
3.4.19.13
2.3.2.2
3.4.19.13
2.3.2.2
3.4.19.13
2.3.2.2
3.4.19.13
2.3.2.2
3.4.19.13
2.3.2.2
3.4.19.13
2.3.2.2
3.4.19.13
2.3.2.2
3.4.19.13
2.3.2.2
3.4.19.13
2.3.2.2
3.4.19.13
Compound (5-L-Glutamyl)-peptide Glutathione Amino acid H2O Peptide Cys-Gly 5-L-Glutamyl amino acid L-Glutamate (5-L-Glutamyl)-peptide-NterminalThr-enzyme tetrahedral-transition-state Gultathione-NterminalThr-enzyme tetrahedral-transition-state Gamma-glutamyl-NterminalThr-acyl-enzyme intermediate Gamma-glutamyl-NterminalThr-AA-enzyme tetrahedral-transition-state Gamma-glutamyl-NterminalThr-enzyme tetrahedral-transition-state
Type amine group,carboxyl group,peptide/protein amino acids,carboxyl group,peptide/protein,sulfhydryl group amino acids H2O peptide/protein amide group,amine group,carboxyl group,sulfhydryl group amide group,amine group,carboxyl group amino acids,carboxyl group
ChEBI 16856
 16856
 		15377
 15377
 		4047
 61694
 4047
 61694
 		16015
 16015
PubChem 124886
 25246407
 124886
 25246407
 		22247451
 962
 22247451
 962
 		439498
 7098621
 439498
 7098621
 		33032
 44272391
 88747398
 33032
 44272391
 88747398
2dbuA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dbuC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dbwA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dbwC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dbxA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dbxC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dg5A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dg5C01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2e0wA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2e0wB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2e0xA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2e0xC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2e0yA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2e0yC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2z8iA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2z8iC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2z8jA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2z8jC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2z8kA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2z8kC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2v36A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2v36C01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3a75A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3a75C01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3whqA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3whrA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3whsA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
4ottA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
4otuA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2nqoA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2nqoC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2qm6A01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2qm6C01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2qmcA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2qmcC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3fnmA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3fnmC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dbuA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dbuC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dbwA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dbwC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dbxA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dbxC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dg5A02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dg5C02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2e0wA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2e0wB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2e0xA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2e0xC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2e0yA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2e0yC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2z8iA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2z8iC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2z8jA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2z8jC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2z8kA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2z8kC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2v36A02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2v36C02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3a75A02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3a75C02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3whqA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3whrA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3whsA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
4ottA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
4otuA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2nqoA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2nqoC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2qm6A02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2qm6C02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2qmcA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2qmcC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3fnmA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3fnmC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dbuB00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dbuD00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2dbwB00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-bound:GGL Unbound Unbound
2dbwD00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-bound:GGL Unbound Unbound
2dbxB00 Unbound Unbound Unbound Unbound Unbound Unbound Bound:GLU Unbound Unbound Unbound Unbound Unbound
2dbxD00 Unbound Unbound Unbound Unbound Unbound Unbound Bound:GLU Unbound Unbound Unbound Unbound Unbound
2dg5B00 Unbound Unbound Unbound Unbound Unbound Unbound Bound:GLU Unbound Unbound Unbound Unbound Unbound
2dg5D00 Unbound Unbound Unbound Unbound Unbound Unbound Bound:GLU Unbound Unbound Unbound Unbound Unbound
2e0xB00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2e0xD00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2e0yB00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2e0yD00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2z8iB00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:AZS
2z8iD00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:AZS
2z8jB00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:AZS Unbound
2z8jD00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:AZS Unbound
2z8kB00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:AVN Unbound Unbound
2z8kD00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:AVN Unbound Unbound
2v36B00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2v36D00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3a75B00 Unbound Unbound Unbound Unbound Unbound Unbound Bound:GLU Unbound Unbound Unbound Unbound Unbound
3a75D00 Unbound Unbound Unbound Unbound Unbound Unbound Bound:GLU Unbound Unbound Unbound Unbound Unbound
3whqB00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3whrB00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3whsB00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:AVN Unbound Unbound
4ottB00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
4otuB00 Unbound Unbound Unbound Unbound Unbound Unbound Bound:GLU Unbound Unbound Unbound Unbound Unbound
2nqoB00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2nqoD00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2qm6B00 Unbound Unbound Unbound Unbound Unbound Unbound Bound:GLU Unbound Unbound Unbound Unbound Unbound
2qm6D00 Unbound Unbound Unbound Unbound Unbound Unbound Bound:GLU Unbound Unbound Unbound Unbound Unbound
2qmcB00 Unbound Analogue:GTB Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2qmcD00 Unbound Analogue:GTB Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3fnmB00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:AVN Unbound Unbound
3fnmD00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:AVN Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature[9],[10],[19]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
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
2dbuB00 THR 391;THR 409 THR 391;GLY 483;GLY 484
2dbuD00 THR 391;THR 409 THR 391;GLY 483;GLY 484
2dbwB00 THR 391;THR 409 THR 391;GLY 483;GLY 484
2dbwD00 THR 391;THR 409 THR 391;GLY 483;GLY 484
2dbxB00 THR 391;THR 409 THR 391;GLY 483;GLY 484
2dbxD00 THR 391;THR 409 THR 391;GLY 483;GLY 484
2dg5B00 THR 391;THR 409 THR 391;GLY 483;GLY 484
2dg5D00 THR 391;THR 409 THR 391;GLY 483;GLY 484
2e0xB00 THR 391;THR 409 THR 391;GLY 483;GLY 484
2e0xD00 THR 391;THR 409 THR 391;GLY 483;GLY 484
2e0yB00 THR 391;THR 409 THR 391;GLY 483;GLY 484
2e0yD00 THR 391;THR 409 THR 391;GLY 483;GLY 484
2z8iB00 THR 391;THR 409 THR 391;GLY 483;GLY 484
2z8iD00 THR 391;THR 409 THR 391;GLY 483;GLY 484
2z8jB00 THR 391;THR 409 THR 391;GLY 483;GLY 484
2z8jD00 THR 391;THR 409 THR 391;GLY 483;GLY 484
2z8kB00 THR 391;THR 409 THR 391;GLY 483;GLY 484
2z8kD00 THR 391;THR 409 THR 391;GLY 483;GLY 484
2v36B00 THR 403;THR 421 THR 403;GLY 485;GLY 486
2v36D00 THR 403;THR 421 THR 403;GLY 485;GLY 486
3a75B00 THR 403;THR 421 THR 403;GLY 485;GLY 486
3a75D00 THR 403;THR 421 THR 403;GLY 485;GLY 486
3whqB00 THR 403;THR 421 THR 403;GLY 485;GLY 486
3whrB00 THR 403;THR 421 THR 403;GLY 485;GLY 486
3whsB00 THR 403;THR 421 THR 403;GLY 485;GLY 486
4ottB00 THR 399;THR 417 THR 399;GLY 481;GLY 482
4otuB00 THR 399;THR 417 THR 399;GLY 481;GLY 482
2nqoB00 THR 380;THR 398 THR 380;GLY 472;GLY 473
2nqoD00 THR 380;THR 398 THR 380;GLY 472;GLY 473
2qm6B00 THR 380;THR 398 THR 380;GLY 472;GLY 473
2qm6D00 THR 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
3fnmB00 THR 380;THR 398 THR 380;GLY 472;GLY 473
3fnmD00 THR 380;THR 398 THR 380;GLY 472;GLY 473

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[10]
p.6473-6474
[12]
Fig.6, p.540

References
[1]
Resource
Comments
Medline ID
PubMed ID 7903400
Journal J Mol Biol
Year 1993
Volume 234
Pages 1259-62
Authors Kumagai H, Nohara S, Suzuki H, Hashimoto W, Yamamoto K, Sakai H, Sakabe K, Fukuyama K, Sakabe N
Title Crystallization and preliminary X-ray analysis of gamma-glutamyltranspeptidase from Escherichia coli K-12.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 7818493
Journal Biochem J
Year 1994
Volume 304
Pages 869-76
Authors Gololobov MYu, Bateman RC Jr
Title gamma-Glutamyltranspeptidase-catalysed acyl-transfer to the added acceptor does not proceed via the ping-pong mechanism.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 8864839
Journal J Biochem
Year 1996
Volume 120
Pages 26-8
Authors Sakai H, Sakabe N, Sasaki K, Hashimoto W, Suzuki H, Tachi H, Kumagai H, Sakabe K
Title A preliminary description of the crystal structure of gamma-glutamyltranspeptidase from E. coli K-12.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 12207027
Journal J Biol Chem
Year 2002
Volume 277
Pages 43536-43
Authors Suzuki H, Kumagai H
Title Autocatalytic processing of gamma-glutamyltranspeptidase.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 14516202
Journal Biochemistry
Year 2003
Volume 42
Pages 11504-13
Authors Castonguay R, Lherbet C, Keillor JW
Title Kinetic studies of rat kidney gamma-glutamyltranspeptidase deacylation reveal a general base-catalyzed mechanism.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 12643897
Journal Bioorg Med Chem Lett
Year 2003
Volume 13
Pages 997-1000
Authors Lherbet C, Morin M, Castonguay R, Keillor JW
Title Synthesis of aza and oxaglutamyl-p-nitroanilide derivatives and their kinetic studies with gamma-glutamyltranspeptidase.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 15466585
Journal Appl Environ Microbiol
Year 2004
Volume 70
Pages 6324-8
Authors Suzuki H, Miwa C, Ishihara S, Kumagai H
Title A single amino acid substitution converts gamma-glutamyltranspeptidase to a class IV cephalosporin acylase (glutaryl-7-aminocephalosporanic acid acylase).
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 16399402
Journal Methods Enzymol
Year 2005
Volume 401
Pages 449-67
Authors Keillor JW, Castonguay R, Lherbet C
Title Gamma-glutamyl transpeptidase substrate specificity and catalytic mechanism.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 16672227
Journal J Biol Chem
Year 2006
Volume 281
Pages 19029-37
Authors Boanca G, Sand A, Barycki JJ
Title Uncoupling the enzymatic and autoprocessing activities of Helicobacter pylori gamma-glutamyltranspeptidase.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 16618936
Journal Proc Natl Acad Sci U S A
Year 2006
Volume 103
Pages 6471-6
Authors Okada T, Suzuki H, Wada K, Kumagai H, Fukuyama K
Title Crystal structures of gamma-glutamyltranspeptidase from Escherichia coli, a key enzyme in glutathione metabolism, and its reaction intermediate.
Related PDB 2dbu 2dbw 2dbx 2dg5
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 17960917
Journal Biochemistry
Year 2007
Volume 46
Pages 13407-14
Authors Morrow AL, Williams K, Sand A, Boanca G, Barycki JJ
Title Characterization 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 PDB 2qm6 2qmc
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 17107958
Journal J Biol Chem
Year 2007
Volume 282
Pages 534-41
Authors Boanca G, Sand A, Okada T, Suzuki H, Kumagai H, Fukuyama K, Barycki JJ
Title Autoprocessing of Helicobacter pylori gamma-glutamyltranspeptidase leads to the formation of a threonine-threonine catalytic dyad.
Related PDB 2nqo
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 17135273
Journal J Biol Chem
Year 2007
Volume 282
Pages 2433-9
Authors Okada T, Suzuki H, Wada K, Kumagai H, Fukuyama K
Title Crystal structure of the gamma-glutamyltranspeptidase precursor protein from Escherichia coli. Structural changes upon autocatalytic processing and implications for the maturation mechanism.
Related PDB 2e0w 2e0x 2e0y
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 18036555
Journal Biochem Biophys Res Commun
Year 2008
Volume 366
Pages 294-300
Authors Ong PL, Yao YF, Weng YM, Hsu WH, Lin LL
Title Residues Arg114 and Arg337 are critical for the proper function of Escherichia coli gamma-glutamyltranspeptidase.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 18555071
Journal J Mol Biol
Year 2008
Volume 380
Pages 361-72
Authors Wada K, Hiratake J, Irie M, Okada T, Yamada C, Kumagai H, Suzuki H, Fukuyama K
Title Crystal structures of Escherichia coli gamma-glutamyltranspeptidase in complex with azaserine and acivicin: novel mechanistic implication for inhibition by glutamine antagonists.
Related PDB 2z8i 2z8j 2z8k
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 19256527
Journal Biochemistry
Year 2009
Volume 48
Pages 2459-67
Authors Williams K, Cullati S, Sand A, Biterova EI, Barycki JJ
Title Crystal structure of acivicin-inhibited gamma-glutamyltranspeptidase reveals critical roles for its C-terminus in autoprocessing and catalysis.
Related PDB 3fnm
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 19788059
Journal Indian J Biochem Biophys
Year 2009
Volume 46
Pages 281-8
Authors Hsu WH, Ong PL, Chen SC, Lin LL
Title Contribution of Ser463 residue to the enzymatic and autoprocessing activities of Escherichia coli gamma-glutamyltranspeptidase.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 20572278
Journal Biotechnol J
Year 2010
Volume 5
Pages 829-37
Authors Suzuki H, Yamada C, Kijima K, Ishihara S, Wada K, Fukuyama K, Kumagai H
Title Enhancement of glutaryl-7-aminocephalosporanic acid acylase activity of gamma-glutamyltranspeptidase of Bacillus subtilis.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 20088880
Journal FEBS J
Year 2010
Volume 277
Pages 1000-9
Authors Wada K, Irie M, Suzuki H, Fukuyama K
Title Crystal structure of the halotolerant gamma-glutamyltranspeptidase from Bacillus subtilis in complex with glutamate reveals a unique architecture of the solvent-exposed catalytic pocket.
Related PDB 3a75
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 21298394
Journal Extremophiles
Year 2011
Volume 15
Pages 259-70
Authors Castellano I, Di Salle A, Merlino A, Rossi M, La Cara F
Title Gene cloning and protein expression of ƒÁ-glutamyltranspeptidases from Thermus thermophilus and Deinococcus radiodurans: comparison of molecular and structural properties with mesophilic counterparts.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 22664192
Journal Enzyme Microb Technol
Year 2012
Volume 51
Pages 86-94
Authors Hu HY, Yang JC, Chen JH, Chi MC, Lin LL
Title Enzymatic characterization of Bacillus licheniformis ƒÁ-glutamyltranspeptidase fused with N-terminally truncated forms of Bacillus sp. TS-23 ƒ¿-amylase.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 23036908
Journal Biochim Biophys Acta
Year 2013
Volume 1834
Pages 149-57
Authors Pica A, Russo Krauss I, Castellano I, La Cara F, Graziano G, Sica F, Merlino A
Title Effect of NaCl on the conformational stability of the thermophilic ƒÁ-glutamyltranspeptidase from Geobacillus thermodenitrificans: Implication for globular protein halotolerance.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 24531494
Journal Acta Crystallogr D Biol Crystallogr
Year 2014
Volume 70
Pages 607-14
Authors Ida T, Suzuki H, Fukuyama K, Hiratake J, Wada K
Title Structure 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 PDB 3whq 3whr 3whs
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 24780583
Journal Biochim Biophys Acta
Year 2014
Volume 1844
Pages 1523-9
Authors Lin LL, Chen YY, Chi MC, Merlino A
Title Low 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 PDB 4ott 4otu
Related UniProtKB

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]).

Created Updated
2013-08-10 2015-10-27