| IED ID | IndEnz0002016000 |
| Enzyme Type ID | protease016000 |
| Protein Name |
Glutathione hydrolase proenzyme EC 3.4.19.13 Gamma-glutamyltranspeptidase proenzyme GGT EC 2.3.2.2 Cleaved into: Glutathione hydrolase large chain; Glutathione hydrolase small chain |
| Gene Name | ggt b3447 JW3412 |
| Organism | Escherichia coli (strain K12) |
| Taxonomic Lineage | cellular organisms Bacteria Proteobacteria Gammaproteobacteria Enterobacterales Enterobacteriaceae Escherichia Escherichia coli Escherichia coli (strain K12) |
| Enzyme Sequence | MIKPTFLRRVAIAALLSGSCFSAAAAPPAPPVSYGVEEDVFHPVRAKQGMVASVDATATQVGVDILKEGGNAVDAAVAVGYALAVTHPQAGNLGGGGFMLIRSKNGNTTAIDFREMAPAKATRDMFLDDQGNPDSKKSLTSHLASGTPGTVAGFSLALDKYGTMPLNKVVQPAFKLARDGFIVNDALADDLKTYGSEVLPNHENSKAIFWKEGEPLKKGDTLVQANLAKSLEMIAENGPDEFYKGTIAEQIAQEMQKNGGLITKEDLAAYKAVERTPISGDYRGYQVYSMPPPSSGGIHIVQILNILENFDMKKYGFGSADAMQIMAEAEKYAYADRSEYLGDPDFVKVPWQALTNKAYAKSIADQIDINKAKPSSEIRPGKLAPYESNQTTHYSVVDKDGNAVAVTYTLNTTFGTGIVAGESGILLNNQMDDFSAKPGVPNVYGLVGGDANAVGPNKRPLSSMSPTIVVKDGKTWLVTGSPGGSRIITTVLQMVVNSIDYGLNVAEATNAPRFHHQWLPDELRVEKGFSPDTLKLLEAKGQKVALKEAMGSTQSIMVGPDGELYGASDPRSVDDLTAGY |
| Enzyme Length | 580 |
| Uniprot Accession Number | P18956 |
| Absorption | |
| Active Site | ACT_SITE 391; /note="Nucleophile"; /evidence="ECO:0000269|PubMed:16618936, ECO:0000269|PubMed:18555071" |
| Activity Regulation | ACTIVITY REGULATION: Transferase and hydrolase activities are inhibited by L-Ala and L-Gln, and also by GGT affinity labeling reagents such as azaserine and 6-diazo-5-oxo-nor-leucine. {ECO:0000269|PubMed:2877974}. |
| Binding Site | BINDING 114; /note=Glutamate; /evidence=ECO:0000269|PubMed:16618936; BINDING 409; /note=Glutamate; /evidence=ECO:0000269|PubMed:16618936; BINDING 411; /note=Glutamate; /evidence=ECO:0000269|PubMed:16618936; BINDING 430; /note=Glutamate; /evidence=ECO:0000269|PubMed:16618936; BINDING 433; /note=Glutamate; /evidence=ECO:0000269|PubMed:16618936 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=an alpha-amino acid + an N-terminal (5-L-glutamyl)-[peptide] = 5-L-glutamyl amino acid + N-terminal L-alpha-aminoacyl-[peptide]; Xref=Rhea:RHEA:23904, Rhea:RHEA-COMP:9780, Rhea:RHEA-COMP:9795, ChEBI:CHEBI:77644, ChEBI:CHEBI:78597, ChEBI:CHEBI:78599, ChEBI:CHEBI:78608; EC=2.3.2.2; Evidence={ECO:0000269|PubMed:1360205}; CATALYTIC ACTIVITY: Reaction=glutathione + H2O = L-cysteinylglycine + L-glutamate; Xref=Rhea:RHEA:28807, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985, ChEBI:CHEBI:57925, ChEBI:CHEBI:61694; EC=3.4.19.13; Evidence={ECO:0000305|PubMed:2877974}; CATALYTIC ACTIVITY: Reaction=an S-substituted glutathione + H2O = an S-substituted L-cysteinylglycine + L-glutamate; Xref=Rhea:RHEA:59468, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985, ChEBI:CHEBI:90779, ChEBI:CHEBI:143103; EC=3.4.19.13; Evidence={ECO:0000305|PubMed:2877974}; |
| DNA Binding | |
| EC Number | 3.4.19.13; 2.3.2.2 |
| Enzyme Function | FUNCTION: Cleaves the gamma-glutamyl bond of periplasmic glutathione (gamma-Glu-Cys-Gly), glutathione conjugates, and other gamma-glutamyl compounds. The metabolism of glutathione releases free glutamate and the dipeptide cysteinyl-glycine, which is hydrolyzed to cysteine and glycine by dipeptidases; it may function in amino acid uptake/salvage, or possibly in peptidoglycan linkage. Catalyzes the hydrolysis and transpeptidation of many gamma-glutamyl compounds (including some D-gamma-glutamyl substrates), with a preference for basic and aromatic amino acids as acceptors (PubMed:2877974). The KM values for gamma-glutamyl acceptors are so high that it has been proposed transpeptidation is not the physiological role in E.coli (PubMed:2877974, PubMed:8104180). {ECO:0000269|PubMed:2877974, ECO:0000305|PubMed:8104180}. |
| Temperature Dependency | BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 50 degrees Celsius for both transferase and hydrolase activities. {ECO:0000269|PubMed:2877974}; |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 8.73 for transfer of p-nitroanilide from gamma-GpNA to gly-gly and 9.25 for hydrolysis of gamma-GpNA. {ECO:0000269|PubMed:2877974}; |
| Pathway | PATHWAY: Sulfur metabolism; glutathione metabolism. |
| nucleotide Binding | |
| Features | Active site (1); Beta strand (20); Binding site (5); Chain (2); Helix (27); Mutagenesis (3); Region (3); Signal peptide (1); Turn (4) |
| Keywords | 3D-structure;Acyltransferase;Direct protein sequencing;Glutathione biosynthesis;Hydrolase;Periplasm;Protease;Reference proteome;Signal;Transferase;Zymogen |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Periplasm {ECO:0000269|PubMed:1360205, ECO:0000269|PubMed:2877974}. |
| Modified Residue | |
| Post Translational Modification | PTM: Cleaved by autocatalysis into a large and a small subunit. {ECO:0000269|PubMed:1360205, ECO:0000269|PubMed:16618936, ECO:0000269|PubMed:17135273, ECO:0000269|PubMed:18555071, ECO:0000269|PubMed:2570061}. |
| Signal Peptide | SIGNAL 1..25; /evidence=ECO:0000269|PubMed:2570061 |
| Structure 3D | X-ray crystallography (11) |
| Cross Reference PDB | 2DBU; 2DBW; 2DBX; 2DG5; 2E0W; 2E0X; 2E0Y; 2Z8I; 2Z8J; 2Z8K; 5B5T; |
| Mapped Pubmed ID | 11552267; 11782200; 12207027; 15690043; 2571648; 27622749; 7903400; |
| Motif | |
| Gene Encoded By | |
| Mass | 61,768 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=35 uM for glutathione transfer to glycylglycine (gly-gly) {ECO:0000269|PubMed:2877974}; KM=35 uM for gamma-glutamyl-p-nitroanilide (gamma-GpNA) transfer to gly-gly {ECO:0000269|PubMed:2877974}; KM=29 uM for glutathione hydrolysis {ECO:0000269|PubMed:2877974}; KM=68 uM for gamma-GpNA hydrolysis {ECO:0000269|PubMed:2877974}; |
| Metal Binding | |
| Rhea ID | RHEA:23904; RHEA:28807; RHEA:59468 |
| Cross Reference Brenda | 2.3.2.2;3.4.19.13; |