Lena Bergmann and Galen Correy used X-ray crystallography as a binding assay.
ABLE turned out to be a generalist, binding 43 fragments in two distinct conformations.
(side note, Nick and Justin Biel started this as COVID hit... but it paused until Lena picked it back up!)
ABLE turned out to be a generalist, binding 43 fragments in two distinct conformations.
(side note, Nick and Justin Biel started this as COVID hit... but it paused until Lena picked it back up!)
Comments
ABLE->FABLE generalist to a specialist sensor with 100-fold turn-on fluorescence enhancement!
- Mutagenesis confirmed Asp49 as the essential active site residue
- Disrupting key orienting H-bonds also eliminated activity
- kcat/KM for analogs scaled with the electron-withdrawing nature of leaving groups
We think this mimics how evolution explores generalist binding sites to generate new functions.
Link to preprint: https://www.biorxiv.org/content/10.1101/2025.01.30.635804v1
We welcome feedback!