Mollner, TA; Isenegger, PG; Josephson, B; Buchanan, C; Lercher, L; Oehlrich, D; Hansen, DF; ... Davis, BG; + view all Mollner, TA; Isenegger, PG; Josephson, B; Buchanan, C; Lercher, L; Oehlrich, D; Hansen, DF; Mohammed, S; Baldwin, AJ; Gouverneur, V; Davis, BG; - view fewer (2021) Post-translational insertion of boron in proteins to probe and modulate function. Nature Chemical Biology 10.1038/s41589-021-00883-7. (In press).

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Abstract

Boron is absent in proteins, yet is a micronutrient. It possesses unique bonding that could expand biological function including modes of Lewis acidity not available to typical elements of life. Here we show that post-translational Cβ–Bγ bond formation provides mild, direct, site-selective access to the minimally sized residue boronoalanine (Bal) in proteins. Precise anchoring of boron within complex biomolecular systems allows dative bond-mediated, site-dependent protein Lewis acid–base-pairing (LABP) by Bal. Dynamic protein-LABP creates tunable inter- and intramolecular ligand–host interactions, while reactive protein-LABP reveals reactively accessible sites through migratory boron-to-oxygen Cβ–Oγ covalent bond formation. These modes of dative bonding can also generate de novo function, such as control of thermo- and proteolytic stability in a target protein, or observation of transient structural features via chemical exchange. These results indicate that controlled insertion of boron facilitates stability modulation, structure determination, de novo binding activities and redox-responsive ‘mutation’.

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