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[Folding@home] An allosteric glue

Posted: Wed Dec 18, 2024 1:38 pm
by BOINC_News

There has been growing interest in developing drugs that bind two or more proteins to “glue” them together.

Tacrolimus (aka FK506) is a famous example.  Tacrolimus is an immune-suppressant that is often used to prevent patients from rejecting organ transplants. It works by inhibiting an enzyme called calcineurin by gluing it to another protein called FKBP. Interestingly, FK506 was not designed to do this. It is a natural product that was isolated from a soil sample. Its surprising mechanism was discovered later, and led to an new field of trying to understand and design new molecular glues.

Now we’ve discovered that another well-known natural product has a surprising mechanism.

A natural product called YM is known to inhibit one type of G proteins without impacting others. This specificity is important because it means that YM, or related compounds, could be used to treat cancer without having nasty side effects.

In a new preprint,...


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