Post-translational insertion of boron in proteins to probe and modulate function.

Autor: Mollner TA; Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK., Isenegger PG; Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK., Josephson B; Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK., Buchanan C; Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK., Lercher L; Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK., Oehlrich D; Neuroscience Medicinal Chemistry, Janssen Research and Development, Beerse, Belgium., Hansen DF; Division of Biosciences, University College London, London, UK., Mohammed S; Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK.; Department of Biochemistry, University of Oxford, Oxford, UK.; The Rosalind Franklin Institute, Oxfordshire, Oxford, UK., Baldwin AJ; Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK.; The Rosalind Franklin Institute, Oxfordshire, Oxford, UK., Gouverneur V; Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK., Davis BG; Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK. Ben.Davis@rfi.ac.uk.; The Rosalind Franklin Institute, Oxfordshire, Oxford, UK. Ben.Davis@rfi.ac.uk.
Jazyk: angličtina
Zdroj: Nature chemical biology [Nat Chem Biol] 2021 Dec; Vol. 17 (12), pp. 1245-1261. Date of Electronic Publication: 2021 Nov 01.
DOI: 10.1038/s41589-021-00883-7
Abstrakt: 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'.
(© 2021. The Author(s).)
Databáze: MEDLINE
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