B6H065 · PRX4_PENRW
- ProteinShort-chain dehydrogenase/reductase prx4
- Geneprx4
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids329 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score3/5
Function
function
Short-chain dehydrogenase/reductase; part of the gene cluster that mediates the biosynthesis of PR-toxin, a bicyclic sesquiterpene belonging to the eremophilane class and acting as a mycotoxin (PubMed:24239699).
The first step of the pathway is catalyzed by the aristolochene synthase which performs the cyclization of trans,trans-farnesyl diphosphate (FPP) to the bicyclic sesquiterpene aristolochene (PubMed:24239699).
Following the formation of aristolochene, the non-oxygenated aristolochene is converted to the trioxygenated intermediate eremofortin B, via 7-epi-neopetasone (PubMed:24239699).
This conversion appears to involve three enzymes, a hydroxysterol oxidase-like enzyme, the quinone-oxidase prx3 that forms the quinone-type-structure in the bicyclic nucleus of aristolochene with the C8-oxo group and the C-3 hydroxyl group, and the P450 monooxygenase prx9 that introduces the epoxide at the double bond between carbons 1 and 2 (By similarity) (PubMed:24239699).
No monoxy or dioxy-intermediates have been reported to be released to the broth, so these three early oxidative reactions may be coupled together (PubMed:24239699).
Eremofortin B is further oxidized by another P450 monooxygenase, that introduces a second epoxide between carbons 7 and 11 prior to acetylation to eremofortin A by the acetyltransferase prx11 (By similarity).
The second epoxidation may be performed by a second P450 monooxygenase (PubMed:24239699).
After the acetylation step, eremofortin A is converted to eremofortin C and then to PR-toxin (PubMed:24239699).
First the conversion of eremofortin A to eremofortin C proceeds by oxidation of the side chain of the molecule at C-12 and is catalyzed by the short-chain oxidoreductase prx1 (PubMed:24239699).
The cytochrome P450 monooxygenase prx8 also plays a role in this step (By similarity).
The primary alcohol formed at C-12 is finally oxidized by the short-chain alcohol dehydrogenase prx4 that forms PR-toxin (PubMed:24239699).
The first step of the pathway is catalyzed by the aristolochene synthase which performs the cyclization of trans,trans-farnesyl diphosphate (FPP) to the bicyclic sesquiterpene aristolochene (PubMed:24239699).
Following the formation of aristolochene, the non-oxygenated aristolochene is converted to the trioxygenated intermediate eremofortin B, via 7-epi-neopetasone (PubMed:24239699).
This conversion appears to involve three enzymes, a hydroxysterol oxidase-like enzyme, the quinone-oxidase prx3 that forms the quinone-type-structure in the bicyclic nucleus of aristolochene with the C8-oxo group and the C-3 hydroxyl group, and the P450 monooxygenase prx9 that introduces the epoxide at the double bond between carbons 1 and 2 (By similarity) (PubMed:24239699).
No monoxy or dioxy-intermediates have been reported to be released to the broth, so these three early oxidative reactions may be coupled together (PubMed:24239699).
Eremofortin B is further oxidized by another P450 monooxygenase, that introduces a second epoxide between carbons 7 and 11 prior to acetylation to eremofortin A by the acetyltransferase prx11 (By similarity).
The second epoxidation may be performed by a second P450 monooxygenase (PubMed:24239699).
After the acetylation step, eremofortin A is converted to eremofortin C and then to PR-toxin (PubMed:24239699).
First the conversion of eremofortin A to eremofortin C proceeds by oxidation of the side chain of the molecule at C-12 and is catalyzed by the short-chain oxidoreductase prx1 (PubMed:24239699).
The cytochrome P450 monooxygenase prx8 also plays a role in this step (By similarity).
The primary alcohol formed at C-12 is finally oxidized by the short-chain alcohol dehydrogenase prx4 that forms PR-toxin (PubMed:24239699).
Pathway
Sesquiterpene biosynthesis.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 58 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 60 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Binding site | 81 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 98 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 121 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 161 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Active site | 194 | Proton acceptor | ||||
Sequence: Y | ||||||
Binding site | 194 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Active site | 198 | Lowers pKa of active site Tyr | ||||
Sequence: K | ||||||
Binding site | 198 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 229 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: T |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | membrane | |
Molecular Function | oxidoreductase activity |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameShort-chain dehydrogenase/reductase prx4
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Penicillium > Penicillium chrysogenum species complex
Accessions
- Primary accessionB6H065
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 | 238-258 | Helical | ||||
Sequence: GPLMAAGLPVSSAHMVGLAVV |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for signal, chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-21 | |||||
Sequence: MIPRWQPASIALLLHLDTLRC | ||||||
Chain | PRO_5002845320 | 22-329 | Short-chain dehydrogenase/reductase prx4 | |||
Sequence: HHVSVRPPRATMTSLSIKEEDIPRLDGKVVVISGGASGIGLAAANIFARAGAKIFLFDRNPPDSGEAPENSTFIKADVTSWAELKAAFAQAGHVDIAVANAGVSEEQPYFEDTFDEQGELKEPGFAVVDVNFKGTVMFTKLAVSYMRKQGKGGSVVITASATGYAPEQNLPVYSAIKSGLVGLVRSLRSTLPRFDISINAVAPAATITKLLPMDIAGPLMAAGLPVSSAHMVGLAVVYSAVARQPRMVETYGKENMLDLESKWNGRTILTLGEHYTELEEKLADLRPVWFGWRNTDLTKKQQATADFR | ||||||
Glycosylation | 91 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
PTM databases
Expression
Induction
Expression and the subsequent production of PR-toxin take place under static culture conditions (oxygen limited), whereas no expression of the PR-toxin genes occurs under the strongly aerated conditions required for optimal penicillin production (PubMed:24239699).
There is a negative control of the transcription of the PR-toxin genes by the penicillin biosynthesis gene product(s), or by a regulatory peptide encoded by a small ORF inside the penicillin gene cluster (PubMed:24239699).
There is a negative control of the transcription of the PR-toxin genes by the penicillin biosynthesis gene product(s), or by a regulatory peptide encoded by a small ORF inside the penicillin gene cluster (PubMed:24239699).
Interaction
Protein-protein interaction databases
Structure
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length329
- Mass (Da)35,582
- Last updated2008-12-16 v1
- Checksum055D5E2B85A2CF36
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AM920427 EMBL· GenBank· DDBJ | CAP80260.1 EMBL· GenBank· DDBJ | Genomic DNA |