Sirtuin‐Derived Covalent Binder for the Selective Recognition of Protein Crotonylation.

Lysine crotonylation (Kcr) is increasingly recognized as a key protein post‐translational modification. However, selective detection and enrichment of crotonylated proteins remains a challenging task. Herein we present a covalent binder for the selective recognition of protein crotonylation. Based on proximity‐induced crosslinking, a bacterial sirtuin (CobB) was remodeled with genetically installed thiol‐bearing noncanonical amino acids at the Kcr‐interacting site, which subsequently could react with Kcr sites in a unique NAD+‐dependent manner. The covalent binder has been used to selectively recognize crotonylated proteins in extracted histone samples and in fixed cells. [ABSTRACT FROM AUTHOR]