A new dual-purpose enzyme has been found in sunflowers. As well as slicing proteins, it can glue them together. The discovery provides a starting point for making custom enzymes that join proteins together – which could be useful in designing therapeutic drugs.
AEP (asparaginyl endo-peptidase) enzymes are found in all plants. Their job is to defend plants from pathogens and to mature proteins found in seed stores. But in sunflowers, AEP enzymes appear to have evolved to have a more specialised role, report researchers from the universities of Western Australia in Perth (UWA) and Queensland – to produce a small cyclic and stable peptide (SFT1).
The team discovered that some AEP enzymes can convert parent molecular ‘string’ into a stable ‘bracelet-like’ protein ring (J. S. Mylne et al, doi: http://dx.doi.org/10.1016/j.chembiol.2015.04.010). To make the critical bond to form the ring, AEP allows a cutting and a ligation reaction – where two ends of DNA or RNA are covalently linked – to happen at the same time.
‘The way AEP does this is really interesting,’ remarks lead author Kalia Bernath-Levin of UWA; generally, it’s much easier – takes less energy – for an enzyme to cut proteins than join them.
To confirm AEP can directly perform the dual reaction, the team produced several recombinant plant AEP enzymes in E. coli, and one from jack bean plants. They found the enzymes catalysed both a typical cleavage reaction and a ‘transpeptidation’ reaction where molecules are joined together to create the cyclic peptide.
‘The reaction isn’t really ligation as the energy for it comes from cutting at the same time,’ explains team leader Joshua Mylne. ‘It’s a mouthful, but we’re calling it a cleavage-dependent intramolecular transpeptidation reaction, which basically means a cutting and a ligation reaction happening at the same time [to] make the critical bond.’
He suggests that these ligating enzymes evolved to enable plants like sunflower and jack bean to stabilise bioactive peptides. The researchers think this may give their seeds greater protection from insects.
Mylne says they are ‘desperate’ to know how AEP changed to allow it to do this reaction. ‘Looking at its sequence, you’d just expect this ligating AEP to be like any other protein-cutter,’ he adds.