Cysteine peptidase

Cysteine peptidases are a large family of proteolytic enzymes characterized by a catalytic cysteine residue at their active site[7][2][1]. They are crucial for intracellular protein degradation, mainly operating in lysosomes as part of the endo-lysosomal system[1][2]. Members include papain and the lysosomal cathepsins (such as cathepsin B, L, K, S, and others)[3][7]. Their structure typically consists of two domains (left and right) forming a cleft where the active site, composed of cysteine and histidine residues, is located[2][6][1]. Cysteine peptidases act in various biological processes, including general protein turnover, antigen processing for immune presentation, regulation of cell death (apoptosis), and extracellular matrix remodeling[1][2]. Dysregulation or overexpression of specific cysteine peptidases is implicated in a wide range of diseases, such as cancer metastasis, inflammation, infections, and degenerative diseases[1][2][7]. Selective inhibitors, both protein-based (like cystatin F) and small molecules (e.g., cathepsin K inhibitors), are under study or in clinical use for conditions like osteoporosis, but targeting these enzymes remains challenging due to broad substrate specificity and essential physiological roles[2][1].

Other names

Cysteine proteaseThiol proteasePapain-like peptidaseCysteine cathepsin (includes Cathepsin B, L, K, S, etc.)

Inhibition of the proteolytic active site (usually targeting the catalytic cysteine residue), Allosteric inhibition, Blocking substrate access