Scientists have discovered a new enzyme by chance, according to a paper to be published online this week in Nature Chemical Biology. This discovery highlights the usefulness of small-molecule probes and adds another enzyme to the chemical biology toolbox.
Activity-based probes are small molecules that bind to particular enzymes based on the protein’s function. They have been used to identify new enzymes and to track the activity of large classes of enzymes in cells.
Renier van der Hoorn and colleagues developed a new type of activity-based probe using a reactive beta-lactone that was expected to bind to proteases, or enzymes that cut peptide bonds. The authors hoped to find the beta-lactone probe bound to RD21, a protein thought to be a protease. Instead, they found the probe attached to the N terminus of a different protein. Subsequent biochemical work showed that RD21 had connected the probe and the protein, and can therefore form peptide bonds.
Further work is needed to determine whether RD21 naturally forms these bonds, but in the meantime, the protein will be useful for labelling strategies in chemical biology research more broadly.