Evidence supporting a catalytic pentad mechanism for the proteasome and other N-terminal nucleophile enzymes.

ABSTRACT: Proteases are defined by their nucleophile but require additional residues to regulate their active sites, most often arranged as catalytic triads that control the generation and resolution of acyl-enzyme intermediates. Threonine N-terminal nucleophiles represent a diverse family of proteases and transferases that possess two active site nucleophiles, the side chain hydroxyl and the free amino-terminus, and require autocatalytic cleavage of their N-terminal propeptides. Here we provide evidence that the proteasome, which mediates intracellular protein degradation and contains three different threonine protease subunits, utilizes a unique catalytic pentad mechanism. In addition to the previously defined lysine/aspartate pair which regulates threonine's side chain, a second serine/aspartate

SUBMITTER: Fung D 

PROVIDER: S-EPMC11947121 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature