The Lysine Deprotonation Mechanism in a Ubiquitin Conjugating Enzyme.

ABSTRACT: Ubiquitination is a biochemical reaction in which a small protein, ubiquitin (Ub), is covalently linked to a lysine on a target protein. This type of post-translational modification can signal for protein degradation, DNA repair, or inflammation response. Ubiquitination is catalyzed by three families of enzymes: ubiquitin activating enzymes (E1), ubiquitin conjugating enzymes (E2), and ubiquitin ligases (E3). In this study, we focus on the chemical mechanism used by the E2 enzyme, Ubc13, which forms polyubiquitin chains by linking a substrate Ub to Lys63 on a target ubiquitin (Ub*). Initially, Ubc13 is covalently linked to the substrate Ub. Next, Lys63 in the Ub* is deprotonated, becomes an active nucleophile, and attacks the thioester bond in the Ubc13∼Ub conjugate. The deprotonation mech

SUBMITTER: Wathan AJ 

PROVIDER: S-EPMC12105026 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature