AsianScientist (May 14, 2015) – Scientists have discovered an unusual enzyme in an ordinary plant, the sunflower. In a study published in Chemistry & Biology, researchers describe an extraordinary protein-cutting enzyme that has also evolved to glue proteins together, a finding that may be valuable in the production of therapeutic drugs.
The researchers, from the University of Western Australia (UWA) and the University of Queensland (UQ), unraveled the manufacturing route sunflowers use to make a super-stable protein ring, enzymes known as asparaginyl endopeptidases (AEP).
By using artificial proteins that mimic the parent molecule of a drug-like protein from sunflower seeds, the team led by UWA’s Professor Joshua S. Mylne discovered that some AEP enzymes can convert parent molecular ‘string’ into a small, stable ‘bracelet-like’ protein ring. They also discovered a degrading pathway that cleans up any misprocessing and makes the process 100 percent efficient in sunflower seeds.
Although this work is of interest to researchers by providing an understanding of how protein machinery can stabilize proteins, it also provides a starting point for making custom enzymes that can join proteins together.
“You can find AEP enzymes in all plants where they defend plants from pathogens and mature seed store proteins, but in sunflower AEP appears to have specialized to produce a small cyclic peptide that we think protects the seeds from insects,” said lead author, UWA’s Dr. Kalia Bernath-Levin.
“The way AEP does this is really interesting. Enzymes can accelerate reactions in both directions, but many reactions go just one way. For example, making a protein bond needs energy and for the two pieces to be held close together. So it’s much easier for an enzyme to cut proteins than join them.”
Mylne elaborated on the reaction that occurs:
“The reaction isn’t really ligation as the energy for that comes from cutting at the same time. 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 makes the critical bond,” said Mylne, an Australian Research Council (ARC) future fellow at UWA’s School of Chemistry and Biochemistry and the ARC Center for Excellence in Plant Energy Biology.
“Now we’re desperate to know exactly what changes in AEP allowed it to do this reaction because looking at its sequence, you’d just expect this ligating AEP to be like any other protein-cutter.”
The article can be found at: Bernath-Levin et al. (2015) Peptide Macrocyclization By A Bifunctional Endoprotease.
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Source: The University of Western Australia; Photo: longhorndave/Flickr/CC.
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