E9R9Y3 · GLIK_ASPFU
- ProteinGamma-glutamyl cyclotransferase gliK
- GenegliK
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids273 (go to sequence)
- Protein existenceInferred from homology
- Annotation score3/5
Function
function
Gamma-glutamyl cyclotransferase-like protein; part of the gene cluster that mediates the biosynthesis of gliotoxin, a member of the epipolythiodioxopiperazine (ETP) class of toxins characterized by a disulfide bridged cyclic dipeptide (PubMed:15979823, PubMed:21612254).
The first step in gliotoxin biosynthesis is the condensation of serine and phenylalanine to form the cyclo-L-phenylalanyl-L-serine diketopiperazine (DKP) by the NRPS gliP (PubMed:17154540, PubMed:21612254).
GliP is also able to produce the DKP cyclo-L-tryptophanyl-L-serine, suggesting that the substrate specificity of the first adenylation (A) domain in gliP is sufficiently relaxed to accommodate both L-Phe and L-Trp (PubMed:23434416).
The cytochrome P450 monooxygenase gliC has been shown to catalyze the subsequent hydroxylation of the alpha-carbon of L-Phe in cyclo-L-phenylalanyl-L-serine whereas the second cytochrome P450 enzyme, gliF, is presumably involved in the modification of the DKP side chain (PubMed:23434416, PubMed:24039048).
The glutathione S-transferase (GST) gliG then forms a bis-glutathionylated biosynthetic intermediate which is responsible for the sulfurization of gliotoxin (PubMed:21513890, PubMed:21749092).
This bis-glutathionylated intermediate is subsequently processed by the gamma-glutamyl cyclotransferase gliK to remove both gamma-glutamyl moieties (PubMed:22903976, PubMed:24039048).
Subsequent processing via gliI yields a biosynthetic intermediate, which is N-methylated via the N-methyltransferase gliN, before the gliotoxin oxidoreductase gliT-mediated disulfide bridge closure (PubMed:20548963, PubMed:22936680, PubMed:24039048, PubMed:25062268).
GliN-mediated amide methylation confers stability to ETP, damping the spontaneous formation of tri- and tetrasulfides (PubMed:25062268).
Intracellular dithiol gliotoxin oxidized by gliT is subsequently effluxed by gliA (PubMed:26150413).
Gliotoxin contributes to pathogenesis during invasive aspergillosis (PubMed:17601876, PubMed:18199036).
In macrophages and neutrophils, gliotoxin showed inhibition of various different cell functions including cytokine production, antigen presentation, phagocytosis, and production of reactive oxygen species (PubMed:17601876).
The first step in gliotoxin biosynthesis is the condensation of serine and phenylalanine to form the cyclo-L-phenylalanyl-L-serine diketopiperazine (DKP) by the NRPS gliP (PubMed:17154540, PubMed:21612254).
GliP is also able to produce the DKP cyclo-L-tryptophanyl-L-serine, suggesting that the substrate specificity of the first adenylation (A) domain in gliP is sufficiently relaxed to accommodate both L-Phe and L-Trp (PubMed:23434416).
The cytochrome P450 monooxygenase gliC has been shown to catalyze the subsequent hydroxylation of the alpha-carbon of L-Phe in cyclo-L-phenylalanyl-L-serine whereas the second cytochrome P450 enzyme, gliF, is presumably involved in the modification of the DKP side chain (PubMed:23434416, PubMed:24039048).
The glutathione S-transferase (GST) gliG then forms a bis-glutathionylated biosynthetic intermediate which is responsible for the sulfurization of gliotoxin (PubMed:21513890, PubMed:21749092).
This bis-glutathionylated intermediate is subsequently processed by the gamma-glutamyl cyclotransferase gliK to remove both gamma-glutamyl moieties (PubMed:22903976, PubMed:24039048).
Subsequent processing via gliI yields a biosynthetic intermediate, which is N-methylated via the N-methyltransferase gliN, before the gliotoxin oxidoreductase gliT-mediated disulfide bridge closure (PubMed:20548963, PubMed:22936680, PubMed:24039048, PubMed:25062268).
GliN-mediated amide methylation confers stability to ETP, damping the spontaneous formation of tri- and tetrasulfides (PubMed:25062268).
Intracellular dithiol gliotoxin oxidized by gliT is subsequently effluxed by gliA (PubMed:26150413).
Gliotoxin contributes to pathogenesis during invasive aspergillosis (PubMed:17601876, PubMed:18199036).
In macrophages and neutrophils, gliotoxin showed inhibition of various different cell functions including cytokine production, antigen presentation, phagocytosis, and production of reactive oxygen species (PubMed:17601876).
Catalytic activity
- an alpha-(gamma-L-glutamyl)-L-amino acid = 5-oxo-L-proline + an L-alpha-amino acid
Pathway
Mycotoxin biosynthesis.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | membrane | |
Molecular Function | gamma-glutamylcyclotransferase activity | |
Biological Process | gliotoxin biosynthetic process | |
Biological Process | mycotoxin biosynthetic process |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameGamma-glutamyl cyclotransferase gliK
- EC number
- Short namesGGCT gliK
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Aspergillus > Aspergillus subgen. Fumigati
Accessions
- Primary accessionE9R9Y3
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Membrane ; Single-pass membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 227-243 | Helical | ||||
Sequence: WLGWIILTLYGLMWSYH |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000437727 | 1-273 | Gamma-glutamyl cyclotransferase gliK | |||
Sequence: MGKAALQDPHGGIWYFAYGSNLRLSVLENRGIKALDIKAVIVPSHYLTFDIFGIPYAEPSFASVAPFAREKKTTLRLGDSPASRDVPPVQGLAYLLNPRDYRQLVISEGGGVAYDEVEVHASILDKDGKPDPGATLIARTLQAKYPWRPNGAPSARYLGLISTGCKQNEPLTAYSDYIDSLPAYEPPTSLHAKVGGLLFLMFWRPPLRLLIRLIRVNTDQDGHCPQWLGWIILTLYGLMWSYHDNIHSKIWGRGDGRKLHFEETPAKEVPVRH |
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Sequence similarities
Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length273
- Mass (Da)30,501
- Last updated2011-04-05 v1
- Checksum61A9C0A798094BA1
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY838877 EMBL· GenBank· DDBJ | AAW03303.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AAHF01000006 EMBL· GenBank· DDBJ | EAL88821.2 EMBL· GenBank· DDBJ | Genomic DNA |