Recombinant human ECHDC2 is produced in wheat germ expression systems with a glutathione S-transferase (GST) tag for purification and detection . Key structural and functional attributes include:
The protein contains a conserved enoyl-CoA hydratase domain, critical for its putative role in fatty acid metabolism and mitochondrial energy regulation . Structural predictions using AlphaFold indicate a conserved crotonase-like fold, typical of the enoyl-CoA hydratase/isomerase family .
Recombinant ECHDC2 serves as a vital tool in:
Enzyme-Linked Immunosorbent Assays (ELISA) and Western Blotting for protein quantification .
Antibody Production, enabling the generation of specific antibodies (e.g., PA5-55413) .
Functional Studies exploring its role in metabolic pathways and disease .
Mechanism: ECHDC2 deficiency in Brown Norway rats correlates with resistance to myocardial ischemia/reperfusion (I/R) injury, while its overexpression in Dahl S rats exacerbates cell death .
Metabolic Impact: ECHDC2 modulates branched-chain amino acid (BCAA) metabolism, increasing leucine and valine levels, which may influence mitochondrial stress responses .
Tumor Inhibition: Overexpression of ECHDC2 inhibits aerobic glycolysis and proliferation in GC cells by promoting ubiquitin-mediated degradation of MCCC2, a key enzyme in leucine catabolism .
Downstream Effects: ECHDC2 suppresses the P38 MAPK signaling pathway, reducing expression of glycolytic genes PKM2 and GLUT1 (Fig. 1) .
Pathway | Effect of ECHDC2 Overexpression | Citation |
---|---|---|
MCCC2 Stability | Accelerates proteasomal degradation | |
P38 MAPK Signaling | Inhibits activation | |
Aerobic Glycolysis | Reduces lactate production and glucose uptake |
ECHDC2 is highly conserved across species, with 87% sequence identity in mouse and rat orthologs . Functional studies in zebrafish (Danio rerio) and mouse models further validate its role in mitochondrial metabolism .
Current research gaps include elucidating ECHDC2’s precise enzymatic activity and its interactions within mitochondrial metabolic networks. Its therapeutic potential in cancers and cardiovascular diseases warrants further exploration using recombinant protein models .