| IED ID | IndEnz0002018489 |
| Enzyme Type ID | protease018489 |
| Protein Name |
Dipeptidase gliJ EC 3.4.13.19 Gliotoxin biosynthesis protein J |
| Gene Name | gliJ AFUA_6G09650 |
| Organism | Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100) (Aspergillus fumigatus) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Pezizomycotina leotiomyceta Eurotiomycetes Eurotiomycetidae Eurotiales (green and blue molds) Aspergillaceae Aspergillus Aspergillus subgen. Fumigati Neosartorya fumigata (Aspergillus fumigatus) Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100) (Aspergillus fumigatus) |
| Enzyme Sequence | MSPSPIEEQATRLLKEVPLIDGHNDFPYMIRGWFRNDINGQDAHLYDMPIGQTDLQRLQKGLLGGQFWSAFVPCPKNPDKEVGSLEALRQTLQQLDVIHRLIERHPTILQFADSAASIWSSFRAGRVASLIGIEGLHQIADSVSALRMLHRLGVRYVTLTHNCHNAFADAATVSPELHGGLSRKGERLIRELNRMGMMIDLSHTSHEAQTQALRLSRAPVIYSHSSIYSLRAHARNVTDENLHLLHRNRGVVMICFLRELLASEADQATLAHVIDHIIYAGTRIGYEHVGIGSDFDGMLRGPDGLHDVSCYPALVAGLLERGVSEEDVKRVMGLNVIRVLEEVERVAAELQGAGEECLCDELDEVWNEDIKEQLTRERERVRKLGPQK |
| Enzyme Length | 388 |
| Uniprot Accession Number | Q4WMJ8 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | BINDING 161; /note=Substrate; /evidence=ECO:0000255|PROSITE-ProRule:PRU10073; BINDING 235; /note=Substrate; /evidence=ECO:0000255|PROSITE-ProRule:PRU10073; BINDING 294; /note=Substrate; /evidence=ECO:0000255|PROSITE-ProRule:PRU10073 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=an L-aminoacyl-L-amino acid + H2O = 2 an L-alpha-amino acid; Xref=Rhea:RHEA:48940, ChEBI:CHEBI:15377, ChEBI:CHEBI:59869, ChEBI:CHEBI:77460; EC=3.4.13.19; Evidence={ECO:0000255|PROSITE-ProRule:PRU10073}; |
| DNA Binding | |
| EC Number | 3.4.13.19 |
| Enzyme Function | FUNCTION: Dipeptidase; 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:24039048, PubMed:23434416). 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). {ECO:0000269|PubMed:17154540, ECO:0000269|PubMed:18199036, ECO:0000269|PubMed:20548963, ECO:0000269|PubMed:21513890, ECO:0000269|PubMed:21612254, ECO:0000269|PubMed:21749092, ECO:0000269|PubMed:22903976, ECO:0000269|PubMed:22936680, ECO:0000269|PubMed:23434416, ECO:0000269|PubMed:24039048, ECO:0000269|PubMed:25062268}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:15979823}. |
| nucleotide Binding | |
| Features | Beta strand (16); Binding site (3); Chain (1); Disulfide bond (1); Erroneous gene model prediction (1); Helix (20); Metal binding (3); Turn (2) |
| Keywords | 3D-structure;Dipeptidase;Disulfide bond;Hydrolase;Metal-binding;Metalloprotease;Protease;Reference proteome;Virulence;Zinc |
| Interact With | |
| Induction | |
| Subcellular Location | |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (13) |
| Cross Reference PDB | 5LWZ; 5LX0; 5LX1; 5LX4; 5LX7; 5NRT; 5NRU; 5NRX; 5NRY; 5NRZ; 5NS1; 5NS2; 5NS5; |
| Mapped Pubmed ID | 28525266; |
| Motif | |
| Gene Encoded By | |
| Mass | 43,525 |
| Kinetics | |
| Metal Binding | METAL 23; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU10073; METAL 25; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU10073; METAL 134; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU10073 |
| Rhea ID | RHEA:48940 |
| Cross Reference Brenda |