UniProtKB - P13513 (TRI5_FUSSP)
Trichodiene synthase
TRI5
Functioni
Trichodiene synthase; part of the core gene cluster that mediates the biosynthesis of trichothecenes, a very large family of chemically related bicyclic sesquiterpene compounds acting as mycotoxins, including T2-toxin (PubMed:11352533, PubMed:2817906).
The biosynthesis of trichothecenes begins with the cyclization of farnesyl diphosphate to trichodiene and is catalyzed by the trichodiene synthase TRI5 (PubMed:3800398, PubMed:7873527, PubMed:8823172).
Trichodiene undergoes a series of oxygenations catalyzed by the cytochrome P450 monooxygenase TRI4 (PubMed:7651333).
TRI4 controls the addition of four oxygens at C-2, C-3, C-11, and the C-12, C-13-epoxide to form the intermediate isotrichotriol (PubMed:16917519).
Isotrichotriol then undergoes a non-enzymatic isomerization and cyclization to form isotrichodermol (PubMed:2317042).
During this process, the oxygen at the C-2 position becomes the pyran ring oxygen and the hydroxyl group at C-11 is lost (PubMed:2317042).
More complex type A trichothecenes are built by modifying isotrichodermol through a series of paired hydroxylation and acetylation or acylation steps (PubMed:11352533).
Isotrichodermol is converted to isotrichodermin by the acetyltransferase TRI101 (PubMed:10583973).
TRI101 encodes a C-3 transacetylase that acts as a self-protection or resistance factor during biosynthesis and that the presence of a free C-3 hydroxyl group is a key component of Fusarium trichothecene phytotoxicity (PubMed:10583973).
A second hydroxyl group is added to C-15 by the trichothecene C-15 hydroxylase TRI11, producing 15-decalonectrin, which is then acetylated by TRI3, producing calonectrin (PubMed:9435078, PubMed:8593041).
A third hydroxyl group is added at C-4 by the cytochrome P450 monooxygenase TRI13, converting calonectrin to 3,15-diacetoxyspirpenol, which is subsequently acetylated by the acetyltransferase TRI7 (PubMed:12135578, PubMed:11352533).
A fourth hydroxyl group is added to C-8 by the cytochrome P450 monooxygenase TRI1, followed by the addition of an isovaleryl moiety by TRI16 (PubMed:12620849, PubMed:14532047).
Finally, the acetyl group is removed from the C-3 position by the trichothecene C-3 esterase TRI8 to produce T-2 toxin (PubMed:12039755).
12 PublicationsMiscellaneous
Catalytic activityi
- EC:4.2.3.65 Publications
Cofactori
Activity regulationi
Kineticsi
- KM=62.0 nM for farnesyl pyrophosphate2 Publications
- KM=78.0 nM for Mg2+1 Publication
- KM=84.8 nM for Mn2+1 Publication
pH dependencei
: trichothecene biosynthesis Pathwayi
This protein is involved in the pathway trichothecene biosynthesis, which is part of Sesquiterpene biosynthesis.1 PublicationView all proteins of this organism that are known to be involved in the pathway trichothecene biosynthesis and in Sesquiterpene biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 100 | Magnesium 1Combined sources1 Publication | 1 | |
Metal bindingi | 164 | Magnesium 1Combined sources1 Publication | 1 | |
Metal bindingi | 225 | Magnesium 2Combined sources3 Publications | 1 | |
Metal bindingi | 229 | Magnesium 2Combined sources3 Publications | 1 | |
Metal bindingi | 233 | Magnesium 2Combined sources3 Publications | 1 | |
Metal bindingi | 239 | Magnesium 3Combined sources2 Publications | 1 | |
Metal bindingi | 241 | Magnesium 3; via carbonyl oxygenCombined sources2 Publications | 1 | |
Binding sitei | 295 | (4s)-7-azabisabolene; inhibitorCombined sources1 Publication | 1 |
GO - Molecular functioni
- metal ion binding Source: UniProtKB-KW
- trichodiene synthase activity Source: UniProtKB-EC
GO - Biological processi
- sesquiterpenoid biosynthetic process Source: InterPro
Keywordsi
Molecular function | Lyase |
Ligand | Magnesium, Metal-binding |
Enzyme and pathway databases
BRENDAi | 4.2.3.6, 2364 |
UniPathwayi | UPA00267 |
Names & Taxonomyi
Protein namesi | Recommended name: Trichodiene synthase1 Publication (EC:4.2.3.65 Publications)Alternative name(s): Core trichothecene cluster (CTC) protein 51 Publication Sesquiterpene cyclase TRI51 Publication Short name: TS1 Publication |
Gene namesi | Name:TRI51 Publication Synonyms:TOX 5 |
Organismi | Fusarium sporotrichioides |
Taxonomic identifieri | 5514 [NCBI] |
Taxonomic lineagei | Eukaryota › Fungi › Dikarya › Ascomycota › Pezizomycotina › Sordariomycetes › Hypocreomycetidae › Hypocreales › Nectriaceae › Fusarium › |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 100 | D → E: Does not significantly perturb the overall structure of trichodiene synthase but leads to an increased KM, a reduction in kcat, as well as to the production of anomalous sesquiterpene products in addition to trichodiene when incubated with farnesyl diphosphate. 2 Publications | 1 | |
Mutagenesisi | 101 | D → E: Leads to an increased KM for Mg(2+), a reduction in kcat, as well as to the production of anomalous sesquiterpene products in addition to trichodiene when incubated with farnesyl diphosphate. 1 Publication | 1 | |
Mutagenesisi | 104 | D → E: Does not significantly affect the KM and kcat for farnesyl diphosphate. 1 Publication | 1 | |
Mutagenesisi | 146 | C → F: Leads to the loss of activity. 1 Publication | 1 | |
Mutagenesisi | 190 | C → F: Increases the KM for farnesyl diphosphate by about 1.3-fold and reduces the kcat by about 2000-fold. 1 Publication | 1 | |
Mutagenesisi | 225 | N → D: Increases the KM for farnesyl diphosphate by about 6-fold and reduces the kcat by about 28-fold. Leads to complete loss of activity; when associated with S-229. 1 Publication | 1 | |
Mutagenesisi | 229 | S → T: Increases the KM for farnesyl diphosphate by about 77-fold and reduces the kcat by about 9-fold. Leads to complete loss of activity; when associated with D-225. 1 Publication | 1 | |
Mutagenesisi | 295 | Y → F: Does not affect the catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 304 | R → K: Does not cause large changes in the overall structure but increases the KM for farnesyl diphosphate by about 25-fold, reduces the kcat by about 200-fold, and leads to conversion of farnesyl diphosphate not only to trichodiene but to at least 2 additional C(15)H(24) hydrocarbons. 2 Publications | 1 | |
Mutagenesisi | 305 | Y → F: Does not cause large changes in the overall structure but increases the KM for farnesyl diphosphate by about 7-fold. 2 Publications | 1 | |
Mutagenesisi | 305 | Y → T: Increases the KM for farnesyl diphosphate by about 80-fold, reduces the kcat by about 120-fold, and leads to the conversion of farneyl diphosphate to an approximately equal mixture of trichodiene and an unidentified sesquiterpene hydrocarbon. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000221584 | 1 – 374 | Trichodiene synthaseAdd BLAST | 374 |
Expressioni
Inductioni
Structurei
Secondary structure
3D structure databases
SMRi | P13513 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P13513 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 100 – 104 | Aspartate-rich domain1 Publication | 5 |
Sequence similaritiesi
Family and domain databases
Gene3Di | 1.10.600.10, 1 hit |
InterProi | View protein in InterPro IPR008949, Isoprenoid_synthase_dom_sf IPR010458, TRI5_ascomyc IPR024652, Trichodiene_synth |
Pfami | View protein in Pfam PF06330, TRI5, 1 hit |
PIRSFi | PIRSF001388, TRI5, 1 hit |
SFLDi | SFLDG01021, Trichodiene_Synthase_Like, 1 hit |
SUPFAMi | SSF48576, SSF48576, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MENFPTEYFL NTTVRLLEYI RYRDSNYTRE ERIENLHYAY NKAAHHFAQP
60 70 80 90 100
RQQQLLKVDP KRLQASLQTI VGMVVYSWAK VSKECMADLS IHYTYTLVLD
110 120 130 140 150
DSKDDPYPTM VNYFDDLQAG REQAHPWWAL VNEHFPNVLR HFGPFCSLNL
160 170 180 190 200
IRSTLDFFEG CWIEQYNFGG FPGSHDYPQF LRRMNGLGHC VGASLWPKEQ
210 220 230 240 250
FNERSLFLEI TSAIAQMENW MVWVNDLMSF YKEFDDERDQ ISLVKNYVVS
260 270 280 290 300
DEISLHEALE KLTQDTLHSS KQMVAVFSDK DPQVMDTIEC FMHGYVTWHL
310 320 330 340 350
CDRRYRLSEI YEKVKEEKTE DAQKFCKFYE QAANVGAVSP SEWAYPPVAQ
360 370
LANVRSKDVK EVQKPFLSSI ELVE
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF364179 Genomic DNA Translation: AAD13657.1 AF359360 Genomic DNA Translation: AAK33074.1 AY032745 mRNA Translation: AAK77935.1 |
PIRi | JU0064, SYFUTP |
Genome annotation databases
KEGGi | ag:AAD13657 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF364179 Genomic DNA Translation: AAD13657.1 AF359360 Genomic DNA Translation: AAK33074.1 AY032745 mRNA Translation: AAK77935.1 |
PIRi | JU0064, SYFUTP |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1JFA | X-ray | 2.50 | A/B | 1-374 | [»] | |
1JFG | X-ray | 2.50 | A/B | 1-374 | [»] | |
1KIY | X-ray | 2.40 | A/B | 1-374 | [»] | |
1KIZ | X-ray | 2.60 | A/B | 1-374 | [»] | |
1YJ4 | X-ray | 2.30 | A/B | 1-374 | [»] | |
1YYQ | X-ray | 2.10 | A/B | 1-374 | [»] | |
1YYR | X-ray | 2.50 | A/B | 1-374 | [»] | |
1YYS | X-ray | 2.75 | A/B | 1-374 | [»] | |
1YYT | X-ray | 2.90 | A/B | 1-374 | [»] | |
1YYU | X-ray | 2.95 | A/B | 1-374 | [»] | |
2AEK | X-ray | 2.90 | A/B | 1-374 | [»] | |
2AEL | X-ray | 2.50 | A/B | 1-374 | [»] | |
2AET | X-ray | 2.75 | A/B | 1-374 | [»] | |
2PS4 | X-ray | 2.46 | A/B | 1-374 | [»] | |
2PS5 | X-ray | 2.10 | A/B | 1-374 | [»] | |
2PS6 | X-ray | 2.60 | A/B | 1-374 | [»] | |
2PS7 | X-ray | 2.35 | A/B | 1-374 | [»] | |
2PS8 | X-ray | 2.67 | A/B | 1-374 | [»] | |
2Q9Y | X-ray | 2.85 | A/B | 1-374 | [»] | |
2Q9Z | X-ray | 2.95 | A/B | 1-374 | [»] | |
SMRi | P13513 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Genome annotation databases
KEGGi | ag:AAD13657 |
Enzyme and pathway databases
UniPathwayi | UPA00267 |
BRENDAi | 4.2.3.6, 2364 |
Miscellaneous databases
EvolutionaryTracei | P13513 |
Family and domain databases
Gene3Di | 1.10.600.10, 1 hit |
InterProi | View protein in InterPro IPR008949, Isoprenoid_synthase_dom_sf IPR010458, TRI5_ascomyc IPR024652, Trichodiene_synth |
Pfami | View protein in Pfam PF06330, TRI5, 1 hit |
PIRSFi | PIRSF001388, TRI5, 1 hit |
SFLDi | SFLDG01021, Trichodiene_Synthase_Like, 1 hit |
SUPFAMi | SSF48576, SSF48576, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TRI5_FUSSP | |
Accessioni | P13513Primary (citable) accession number: P13513 Secondary accession number(s): Q7LP67 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 1, 1990 |
Last sequence update: | January 1, 1990 | |
Last modified: | September 29, 2021 | |
This is version 98 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Fungal Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencingDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families