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Protein

Glutathione hydrolase proenzyme

Gene

ggt

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).1 Publication1 Publication

Catalytic activityi

A (5-L-glutamyl)-peptide + an amino acid = a peptide + a 5-L-glutamyl amino acid.1 Publication
Glutathione + H2O = L-cysteinylglycine + L-glutamate.1 Publication

Enzyme regulationi

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.1 Publication

Kineticsi

  1. KM=35 µM for glutathione transfer to glycylglycine (gly-gly)1 Publication
  2. KM=35 µM for gamma-glutamyl-p-nitroanilide (gamma-GpNA) transfer to gly-gly1 Publication
  3. KM=29 µM for glutathione hydrolysis1 Publication
  4. KM=68 µM for gamma-GpNA hydrolysis1 Publication

    pH dependencei

    Optimum pH is 8.73 for transfer of p-nitroanilide from gamma-GpNA to gly-gly and 9.25 for hydrolysis of gamma-GpNA.1 Publication

    Temperature dependencei

    Optimum temperature is 50 degrees Celsius for both transferase and hydrolase activities.1 Publication

    Pathwayi: glutathione metabolism

    This protein is involved in the pathway glutathione metabolism, which is part of Sulfur metabolism.
    View all proteins of this organism that are known to be involved in the pathway glutathione metabolism and in Sulfur metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei114Glutamate1 Publication1
    Active sitei391Nucleophile2 Publications1
    Binding sitei409Glutamate1 Publication1
    Binding sitei411Glutamate1 Publication1
    Binding sitei430Glutamate1 Publication1
    Binding sitei433Glutamate1 Publication1

    GO - Molecular functioni

    GO - Biological processi

    • amino acid salvage Source: EcoCyc
    • glutathione biosynthetic process Source: UniProtKB-KW
    • glutathione catabolic process Source: InterPro
    • self proteolysis Source: EcoCyc

    Keywordsi

    Molecular functionAcyltransferase, Hydrolase, Protease, Transferase
    Biological processGlutathione biosynthesis

    Enzyme and pathway databases

    BioCyciEcoCyc:EG10374-MONOMER.
    MetaCyc:EG10374-MONOMER.
    BRENDAi2.3.2.2. 2026.
    3.4.19.13. 2026.
    SABIO-RKiP18956.
    UniPathwayiUPA00204.

    Protein family/group databases

    MEROPSiT03.001.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Glutathione hydrolase proenzyme (EC:3.4.19.131 Publication)
    Alternative name(s):
    Gamma-glutamyltranspeptidase proenzyme1 Publication (EC:2.3.2.21 Publication)
    Short name:
    GGT
    Cleaved into the following 2 chains:
    Gene namesi
    Name:ggt
    Ordered Locus Names:b3447, JW3412
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 Componenti: Chromosome
    • UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG10374. ggt.

    Subcellular locationi

    P18956:

    GO - Cellular componenti

    • outer membrane-bounded periplasmic space Source: EcoCyc
    • periplasmic space Source: EcoliWiki

    Keywords - Cellular componenti

    Periplasm

    Pathology & Biotechi

    Disruption phenotypei

    Loss of growth using exogenous gamma-glutamyl peptides as amino acid sources.1 Publication

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi391T → A: Abolishes autocatalytic cleavage, loss of enzymatic activity. 1 Publication1
    Mutagenesisi513R → A: Not processed into its subunits, loss of enzymatic activity. 1 Publication1
    Mutagenesisi571R → G: Not processed into its subunits, loss of enzymatic activity. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 251 PublicationAdd BLAST25
    ChainiPRO_000001105226 – 390Glutathione hydrolase large chainAdd BLAST365
    ChainiPRO_0000011053391 – 580Glutathione hydrolase small chainAdd BLAST190

    Post-translational modificationi

    Cleaved by autocatalysis into a large and a small subunit.5 Publications

    Keywords - PTMi

    Zymogen

    Proteomic databases

    PaxDbiP18956.
    PRIDEiP18956.

    Interactioni

    Subunit structurei

    This enzyme consists of two polypeptide chains, which are synthesized in precursor form from a single polypeptide.5 Publications

    Protein-protein interaction databases

    BioGridi4261666. 368 interactors.
    DIPiDIP-9758N.
    IntActiP18956. 1 interactor.
    MINTiMINT-1260227.
    STRINGi316385.ECDH10B_3621.

    Structurei

    Secondary structure

    1580
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi39 – 41Combined sources3
    Beta strandi44 – 48Combined sources5
    Beta strandi50 – 54Combined sources5
    Helixi56 – 67Combined sources12
    Helixi72 – 86Combined sources15
    Turni88 – 90Combined sources3
    Beta strandi93 – 102Combined sources10
    Beta strandi108 – 113Combined sources6
    Turni123 – 126Combined sources4
    Beta strandi129 – 131Combined sources3
    Helixi135 – 139Combined sources5
    Helixi142 – 144Combined sources3
    Helixi150 – 161Combined sources12
    Helixi166 – 179Combined sources14
    Helixi185 – 193Combined sources9
    Helixi195 – 197Combined sources3
    Helixi199 – 201Combined sources3
    Helixi203 – 209Combined sources7
    Helixi225 – 237Combined sources13
    Helixi240 – 243Combined sources4
    Helixi246 – 257Combined sources12
    Helixi264 – 269Combined sources6
    Beta strandi273 – 275Combined sources3
    Beta strandi278 – 282Combined sources5
    Beta strandi285 – 289Combined sources5
    Helixi296 – 307Combined sources12
    Helixi312 – 315Combined sources4
    Helixi320 – 340Combined sources21
    Turni344 – 346Combined sources3
    Helixi351 – 354Combined sources4
    Helixi357 – 364Combined sources8
    Helixi375 – 377Combined sources3
    Helixi384 – 386Combined sources3
    Beta strandi392 – 397Combined sources6
    Beta strandi403 – 409Combined sources7
    Turni413 – 416Combined sources4
    Helixi421 – 423Combined sources3
    Helixi430 – 433Combined sources4
    Beta strandi434 – 437Combined sources4
    Beta strandi467 – 471Combined sources5
    Beta strandi474 – 479Combined sources6
    Helixi484 – 486Combined sources3
    Helixi487 – 499Combined sources13
    Helixi505 – 510Combined sources6
    Beta strandi518 – 520Combined sources3
    Beta strandi523 – 525Combined sources3
    Helixi531 – 539Combined sources9
    Beta strandi544 – 546Combined sources3
    Beta strandi554 – 558Combined sources5
    Beta strandi564 – 568Combined sources5
    Beta strandi576 – 579Combined sources4

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2DBUX-ray1.95A/C25-390[»]
    B/D391-580[»]
    2DBWX-ray1.80A/C25-390[»]
    B/D391-580[»]
    2DBXX-ray1.70A/C25-390[»]
    B/D391-580[»]
    2DG5X-ray1.60A/C25-390[»]
    B/D391-580[»]
    2E0WX-ray2.55A/B25-580[»]
    2E0XX-ray1.95A/C25-390[»]
    B/D391-580[»]
    2E0YX-ray2.02A/C25-390[»]
    B/D391-580[»]
    2Z8IX-ray1.65A/C25-390[»]
    B/D391-580[»]
    2Z8JX-ray2.05A/C25-390[»]
    B/D391-580[»]
    2Z8KX-ray1.65A/C25-390[»]
    B/D391-580[»]
    5B5TX-ray1.70A/C25-390[»]
    B/D391-580[»]
    ProteinModelPortaliP18956.
    SMRiP18956.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP18956.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni462 – 463Glutamate binding2
    Regioni483 – 484Glutamate binding2

    Sequence similaritiesi

    Belongs to the gamma-glutamyltransferase family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiENOG4105CFB. Bacteria.
    COG0405. LUCA.
    HOGENOMiHOG000175617.
    InParanoidiP18956.
    KOiK00681.
    PhylomeDBiP18956.

    Family and domain databases

    InterProiView protein in InterPro
    IPR000101. GGT_peptidase.
    IPR029055. Ntn_hydrolases_N.
    PANTHERiPTHR43199. PTHR43199. 1 hit.
    PfamiView protein in Pfam
    PF01019. G_glu_transpept. 1 hit.
    PRINTSiPR01210. GGTRANSPTASE.
    SUPFAMiSSF56235. SSF56235. 1 hit.
    TIGRFAMsiTIGR00066. g_glut_trans. 1 hit.
    PROSITEiView protein in PROSITE
    PS00462. G_GLU_TRANSPEPTIDASE. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P18956-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MIKPTFLRRV AIAALLSGSC FSAAAAPPAP PVSYGVEEDV FHPVRAKQGM
    60 70 80 90 100
    VASVDATATQ VGVDILKEGG NAVDAAVAVG YALAVTHPQA GNLGGGGFML
    110 120 130 140 150
    IRSKNGNTTA IDFREMAPAK ATRDMFLDDQ GNPDSKKSLT SHLASGTPGT
    160 170 180 190 200
    VAGFSLALDK YGTMPLNKVV QPAFKLARDG FIVNDALADD LKTYGSEVLP
    210 220 230 240 250
    NHENSKAIFW KEGEPLKKGD TLVQANLAKS LEMIAENGPD EFYKGTIAEQ
    260 270 280 290 300
    IAQEMQKNGG LITKEDLAAY KAVERTPISG DYRGYQVYSM PPPSSGGIHI
    310 320 330 340 350
    VQILNILENF DMKKYGFGSA DAMQIMAEAE KYAYADRSEY LGDPDFVKVP
    360 370 380 390 400
    WQALTNKAYA KSIADQIDIN KAKPSSEIRP GKLAPYESNQ TTHYSVVDKD
    410 420 430 440 450
    GNAVAVTYTL NTTFGTGIVA GESGILLNNQ MDDFSAKPGV PNVYGLVGGD
    460 470 480 490 500
    ANAVGPNKRP LSSMSPTIVV KDGKTWLVTG SPGGSRIITT VLQMVVNSID
    510 520 530 540 550
    YGLNVAEATN APRFHHQWLP DELRVEKGFS PDTLKLLEAK GQKVALKEAM
    560 570 580
    GSTQSIMVGP DGELYGASDP RSVDDLTAGY
    Length:580
    Mass (Da):61,768
    Last modified:November 1, 1990 - v1
    Checksum:i772F652EBA2A5F00
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M28722 Genomic DNA. Translation: AAA23869.1.
    U18997 Genomic DNA. Translation: AAA58245.1.
    U00096 Genomic DNA. Translation: AAC76472.1.
    AP009048 Genomic DNA. Translation: BAE77846.1.
    U00039 Genomic DNA. Translation: AAB18422.1.
    PIRiJV0028. EKECEX.
    RefSeqiNP_417904.1. NC_000913.3.
    WP_000595082.1. NZ_LN832404.1.

    Genome annotation databases

    EnsemblBacteriaiAAC76472; AAC76472; b3447.
    BAE77846; BAE77846; BAE77846.
    GeneIDi947947.
    KEGGiecj:JW3412.
    eco:b3447.
    PATRICifig|511145.12.peg.3544.

    Similar proteinsi

    Entry informationi

    Entry nameiGGT_ECOLI
    AccessioniPrimary (citable) accession number: P18956
    Secondary accession number(s): Q2M7B0
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
    Last sequence update: November 1, 1990
    Last modified: September 27, 2017
    This is version 156 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Escherichia coli
      Escherichia coli (strain K12): entries and cross-references to EcoGene
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families