Post-translational insertion of boron in proteins to probe and modulate function.
Nat Chem Biol
; 17(12): 1245-1261, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-34725511
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 Cß-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 Cß-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'.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Boro
/
Proteínas
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article