A0A348HAY5 · PHIJ_FUNX7
- ProteinAlkylcitrate synthase phiJ
- GenephiJ
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids457 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score3/5
Function
function
Alkylcitrate synthase; part of the gene cluster that mediates the biosynthesis of the antihypercholesterolemic agents phomoidrides which are dimeric anhydrides (PubMed:26558485).
Within the pathway, the alkylcitrate synthase (ACS) phiJ and the alkylcitrate dehydratase (ACDH) phiI produce the decarboxylated monomeric anhydrides by coupling the C12-fatty acyl product from phiA with oxalacetic acid (PubMed:26558485).
The pathway begins with the highly reducing polyketide synthase phiA that catalyzes the formation of a C12-fatty acyl-ACP, starting from one acetate and 5 malonate units. The hydrolase phiM is involved in the release of the C12-fatty acyl chain from phiA. The alkylcitrate synthase (ACS) phiJ and the alkylcitrate dehydratase (ACDH) phiI then give rise to decarboxylated monomeric anhydrides by coupling the C12-fatty acyl chain with oxalacetic acid. The cyclase phiC is responsible for the dimerization of the monomeric anhydrides which leads to the production of prephomoidride that contains the characteristic bicyclo[4.3.1]deca-1,6-diene system of phomoidrides. Iterative oxidation catalyzed by the alpha-ketoglutarate-dependent dioxygenase phiK produced then phomoidride A. Finally, the methyltransferase phiE converts phomoidride A to phomoidride B via an acetalization reaction. The phosphatidylethanolamine-binding protein phiB and phiN are not essential for dimerization and their functions have still to be determined (Probable)
Within the pathway, the alkylcitrate synthase (ACS) phiJ and the alkylcitrate dehydratase (ACDH) phiI produce the decarboxylated monomeric anhydrides by coupling the C12-fatty acyl product from phiA with oxalacetic acid (PubMed:26558485).
The pathway begins with the highly reducing polyketide synthase phiA that catalyzes the formation of a C12-fatty acyl-ACP, starting from one acetate and 5 malonate units. The hydrolase phiM is involved in the release of the C12-fatty acyl chain from phiA. The alkylcitrate synthase (ACS) phiJ and the alkylcitrate dehydratase (ACDH) phiI then give rise to decarboxylated monomeric anhydrides by coupling the C12-fatty acyl chain with oxalacetic acid. The cyclase phiC is responsible for the dimerization of the monomeric anhydrides which leads to the production of prephomoidride that contains the characteristic bicyclo[4.3.1]deca-1,6-diene system of phomoidrides. Iterative oxidation catalyzed by the alpha-ketoglutarate-dependent dioxygenase phiK produced then phomoidride A. Finally, the methyltransferase phiE converts phomoidride A to phomoidride B via an acetalization reaction. The phosphatidylethanolamine-binding protein phiB and phiN are not essential for dimerization and their functions have still to be determined (Probable)
Catalytic activity
- (2E,10E)-dode-2,10-dicenoyl-CoA + H2O + oxaloacetate = (4E,11E)-2-hydroxytrideca-4,11-dien-1,2,3-tricarboxylate + CoA + H+This reaction proceeds in the forward direction.
Biotechnology
Phomoidrides A and B (also known as CP-225,917 and CP-263,114) are potent inhibitors of Ras farnesyltransferase and squalene synthase (PubMed:9066758).
CP-225,917 and CP-263,114 inhibit Ras farnesyl transferase from rat brain with IC50 values of 6 uM and 20 uoM, respectively (PubMed:9066758).
CP-225,917 inhibits squalene synthase with an IC50 value of 43 uM and CP-263,114 with an IC50 of 160 uM (PubMed:9066758).
CP-225,917 and CP-263,114 inhibit Ras farnesyl transferase from rat brain with IC50 values of 6 uM and 20 uoM, respectively (PubMed:9066758).
CP-225,917 inhibits squalene synthase with an IC50 value of 43 uM and CP-263,114 with an IC50 of 160 uM (PubMed:9066758).
Pathway
Secondary metabolite biosynthesis.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 328 | |||||
Sequence: H | ||||||
Active site | 384 | |||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | mitochondrial matrix | |
Molecular Function | citrate (Si)-synthase activity | |
Biological Process | carbohydrate metabolic process | |
Biological Process | tricarboxylic acid cycle |
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAlkylcitrate synthase phiJ
- EC number
- Short namesACS
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Fungi
Accessions
- Primary accessionA0A348HAY5
Subcellular Location
UniProt Annotation
GO Annotation
Phenotypes & Variants
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000458946 | 1-457 | Alkylcitrate synthase phiJ | |||
Sequence: MALSSQAQGKLFVRDSRTSREYEIPISNNTINAADFQKINLPTKGKSLTKALGLQLYDPGMQNTAIKKTEIIGRDPSTGLPLLRGVTSQELWKRRCDFEELFSLMVFGNYPTIVEREALRYQFAEYMKEVPKVVGSVIRKFPPSSPPLPMITAGLSAYLSSDPDFIPAIHGGNIYHRNPRAADEAAIKTAAVYAVVIGLISCHKKGINFVPADTDDTFLENLFRMCGLVDPATRRPDPHVLAVFRKGLVLNCDNGMTQSNLVLCATASSLCDPISCLISAISAAYGPLHYGAQEAGYRTLSEIGSADRVPHFLEQVKRRERRLFGYGHRTFATEDPRLNAVKGWLQELDFDSKREPLMKIAEEIDRLAAQDDYFTSRGLRANADFYTLFVFRAYGFDWDMIGAANFCMRIIGFMAHWREAMEQEIKIFRARDYYVGPSKKDPNRESSGTGILAQARL |
Expression
Induction
expression is induced under low pH conditions.
Structure
Sequence
- Sequence statusComplete
- Length457
- Mass (Da)51,194
- Last updated2018-11-07 v1
- ChecksumEF52E00506D400FB