P18956 · GGT_ECOLI
- ProteinGlutathione hydrolase proenzyme
- Geneggt
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids580 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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).
Catalytic activity
- an alpha-amino acid + an N-terminal (5-L-glutamyl)-[peptide] = 5-L-glutamyl amino acid + N-terminal L-alpha-aminoacyl-[peptide]
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.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
35 μM | glutathione transfer to glycylglycine (gly-gly) | |||||
35 μM | gamma-glutamyl-p-nitroanilide (gamma-GpNA) | |||||
29 μM | glutathione hydrolysis | |||||
68 μM | gamma-GpNA hydrolysis |
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.
Temperature Dependence
Optimum temperature is 50 degrees Celsius for both transferase and hydrolase activities.
Pathway
Sulfur metabolism; glutathione metabolism.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 114 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Active site | 391 | Nucleophile | ||||
Sequence: T | ||||||
Binding site | 409 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 411 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 430 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 433 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 462-463 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: SS | ||||||
Binding site | 483-484 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: GG |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | outer membrane-bounded periplasmic space | |
Cellular Component | periplasmic space | |
Molecular Function | gamma-glutamyl-peptidase activity | |
Molecular Function | glutathione hydrolase activity | |
Molecular Function | leukotriene C4 gamma-glutamyl transferase activity | |
Biological Process | amino acid salvage | |
Biological Process | glutathione biosynthetic process | |
Biological Process | glutathione catabolic process | |
Biological Process | self proteolysis |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameGlutathione hydrolase proenzyme
- EC number
- Alternative names
- Cleaved into 2 chains
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageBacteria > Pseudomonadota > Gammaproteobacteria > Enterobacterales > Enterobacteriaceae > Escherichia
Accessions
- Primary accessionP18956
- Secondary accessions
Proteomes
Subcellular Location
Phenotypes & Variants
Disruption phenotype
Loss of growth using exogenous gamma-glutamyl peptides as amino acid sources.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 391 | Abolishes autocatalytic cleavage, loss of enzymatic activity. | ||||
Sequence: T → A | ||||||
Mutagenesis | 513 | Not processed into its subunits, loss of enzymatic activity. | ||||
Sequence: R → A | ||||||
Mutagenesis | 571 | Not processed into its subunits, loss of enzymatic activity. | ||||
Sequence: R → G |
PTM/Processing
Features
Showing features for signal, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-25 | |||||
Sequence: MIKPTFLRRVAIAALLSGSCFSAAA | ||||||
Chain | PRO_0000011052 | 26-390 | Glutathione hydrolase large chain | |||
Sequence: APPAPPVSYGVEEDVFHPVRAKQGMVASVDATATQVGVDILKEGGNAVDAAVAVGYALAVTHPQAGNLGGGGFMLIRSKNGNTTAIDFREMAPAKATRDMFLDDQGNPDSKKSLTSHLASGTPGTVAGFSLALDKYGTMPLNKVVQPAFKLARDGFIVNDALADDLKTYGSEVLPNHENSKAIFWKEGEPLKKGDTLVQANLAKSLEMIAENGPDEFYKGTIAEQIAQEMQKNGGLITKEDLAAYKAVERTPISGDYRGYQVYSMPPPSSGGIHIVQILNILENFDMKKYGFGSADAMQIMAEAEKYAYADRSEYLGDPDFVKVPWQALTNKAYAKSIADQIDINKAKPSSEIRPGKLAPYESNQ | ||||||
Chain | PRO_0000011053 | 391-580 | Glutathione hydrolase small chain | |||
Sequence: TTHYSVVDKDGNAVAVTYTLNTTFGTGIVAGESGILLNNQMDDFSAKPGVPNVYGLVGGDANAVGPNKRPLSSMSPTIVVKDGKTWLVTGSPGGSRIITTVLQMVVNSIDYGLNVAEATNAPRFHHQWLPDELRVEKGFSPDTLKLLEAKGQKVALKEAMGSTQSIMVGPDGELYGASDPRSVDDLTAGY |
Post-translational modification
Cleaved by autocatalysis into a large and a small subunit.
Keywords
- PTM
Proteomic databases
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 561-580 | Disordered | ||||
Sequence: DGELYGASDPRSVDDLTAGY |
Sequence similarities
Belongs to the gamma-glutamyltransferase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length580
- Mass (Da)61,768
- Last updated1990-11-01 v1
- Checksum772F652EBA2A5F00
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M28722 EMBL· GenBank· DDBJ | AAA23869.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U18997 EMBL· GenBank· DDBJ | AAA58245.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U00096 EMBL· GenBank· DDBJ | AAC76472.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AP009048 EMBL· GenBank· DDBJ | BAE77846.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U00039 EMBL· GenBank· DDBJ | AAB18422.1 EMBL· GenBank· DDBJ | Genomic DNA |