Global analysis of proteasomal substrate specificity using positional-scanning libraries of covalent inhibitors.

ABSTRACT: The proteasome is a large protease complex consisting of multiple catalytic subunits that function simultaneously to digest protein substrates. This complexity has made deciphering the role each subunit plays in the generation of specific protein fragments difficult. Positional scanning libraries of peptide vinyl sulfones were generated in which the amino acid located directly at the site of hydrolysis (P1 residue) was held constant and sequences distal to that residue (P2, P3, and P4 positions) were varied across all natural amino acids (except cysteine and methionine). Binding information for each of the individual catalytic subunits was obtained for each library under a variety of different conditions. The resulting specificity profiles indicated that substrate positions distal to P1 ar

SUBMITTER: Nazif T 

PROVIDER: S-EPMC30590 | biostudies-literature | 2001 Mar

REPOSITORIES: biostudies-literature