Structure of a Cys25→Ser mutant of human cathepsin S

Cathepsin S (EC 3.4.22.27), a cysteine proteinase of the papain superfamily, plays a critical role in the generation of a major histocompatibility complex (MHC) class II restricted T-­cell response by antigen-presenting cells. Therefore, selective inhibition of this enzyme may be useful in modulating class II restricted T-cell responses in immune-related disorders such as rheumatoid arthritis, multiple sclerosis and extrinsic asthma. The three-dimensional structure at 2.2 Å resolution of the active-site Cys25→Ser mutant presented here in an unliganded state provides further insight useful for the design of selective enzyme inhibitors.