Free-thiol Cys331 exposed during activation process is critical for native tetramer structure of cathepsin C (dipeptidyl peptidase I).

ABSTRACT: The mature bovine cathepsin C (CC) molecule is composed of four identical monomers, each proteolytically processed into three chains. Five intrachain disulfides and three nonpaired cysteine residues per monomer were identified. Beside catalytic Cys234 in the active site, free-thiol Cys331 and Cys424 were characterized. Cys424 can be classified as inaccessible buried residue. Selective modification of Cys331 results in dissociation of native CC tetramer into dimers. The 3D homology-based model of the CC catalytic core suggests that Cys331 becomes exposed as the activation peptide is removed during procathepsin C activation. The model further shows that exposed Cys331 is surrounded by a surface hydrophobic cluster, unique to CC, forming a dimer-dimer interaction interface. Substrate/inhibito

SUBMITTER: Horn M 

PROVIDER: S-EPMC2384168 | biostudies-literature | 2002 Apr

REPOSITORIES: biostudies-literature