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A biomimetic electrostatic assistance for guiding and promoting N-terminal protein chemical modification.

ABSTRACT: The modification of protein electrostatics by phosphorylation is a mechanism used by cells to promote the association of proteins with other biomolecules. In this work, we show that introducing negatively charged phosphoserines in a reactant is a powerful means for directing and accelerating the chemical modification of proteins equipped with oppositely charged arginines. While the extra charged amino acid residues induce no detectable affinity between the reactants, they bring site-selectivity to a reaction that is otherwise devoid of such a property. They also enable rate accelerations of four orders of magnitude in some cases, thereby permitting chemical processes to proceed at the protein level in the low micromolar range, using reactions that are normally too slow to be useful in such dilute conditions.

SUBMITTER: Ollivier N

PROVIDER: S-EPMC9637170 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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A biomimetic electrostatic assistance for guiding and promoting N-terminal protein chemical modification.

Ollivier Nathalie N Sénéchal Magalie M Desmet Rémi R Snella Benoît B Agouridas Vangelis V Melnyk Oleg O

Nature communications 20221105 1

The modification of protein electrostatics by phosphorylation is a mechanism used by cells to promote the association of proteins with other biomolecules. In this work, we show that introducing negatively charged phosphoserines in a reactant is a powerful means for directing and accelerating the chemical modification of proteins equipped with oppositely charged arginines. While the extra charged amino acid residues induce no detectable affinity between the reactants, they bring site-selectivity ...[more]

PMID: 36335111

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