A protein is a chain of amino acids held together by what are called peptide bonds. On their own, those bonds are extremely stable; they're estimated to have a half-life of several hundred years. But in Earth's environment, most proteins don't last nearly that long. That's because organisms have evolved a handful of ways to catalyze the break-up of peptide bonds, which have diversified into countless specialized protein-digesting enzymes. Proteases are everywhere and generally make short work of any proteins that find their way into the environment.

Now, researchers have basically short-circuited the diversification process, using AI-based protein design tools to take the catalytic core of two types of protease and replace the entire rest of the protein. The resulting enzymes could be tuned to cut specific proteins in half, and the researchers demonstrated their effectiveness by using them to cut proteins associated with neurological diseases.

Cutting proteins

The basic peptide bond isn't especially interesting-looking—it's what you get when you link an amino group to an acid, releasing a water molecule in the process. As their name implies, amino acids have both an amino and an acid group, allowing them to form peptide bonds on two sides of the amino acid. This is critical for building up the long chains found in proteins. (The amino acids also have side chains with distinctive chemistry, which gives a backbone specific properties.)

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Honey bees are known to leave their stingers embedded in tender flesh once they sting you and fly away. Scientists have now determined that the stinger is able to continue pumping venom into its unfortunate victim even after the bee flies away, thanks to a unique double-piston pump-like mechanism, according to a new paper published in the Proceedings of the National Academy of Sciences.

Different species have evolved different mechanisms for delivering venom, which involves piercing the skin and then pumping venom from a gland or reservoir. Spiders, for instance, have muscles surrounding their venom glands, which contract and eject venom through hollow fangs. Bees, wasps, and ants deliver venom via their stingers, either by contracting muscles around the venom reservoir or through stiff elements called lancets working together to pump venom.

Honey bees (Apis mellifera) add a unique feature: Worker bees fly away after inserting their stingers in the target, leaving the stinger behind. The stinger continues to penetrate the tissue and pump venom on its own, a rare phenomenon known as autotomy. A honey bee's stinger has three main interlocking elements that form the venom canal: a stylet that widens to form the main pumping chamber and two sharp-tipped lancets that slide back and forth, piercing the tissue and pumping venom into the target. But the precise mechanism by which the pumping action is achieved has never been directly observed.

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