Kallikrein-related peptidase 3 (prostate-specific antigen) (KLK3 (PSA))

Kallikrein-related peptidase 3 (KLK3), commonly known as prostate-specific antigen (PSA), is a serine protease primarily synthesized by prostate epithelial cells and secreted into seminal fluid. Its main physiological role involves hydrolyzing high-molecular-mass proteins like semenogelin-1 and fibronectin in the seminal coagulum, facilitating semen liquefaction and enabling sperm motility post-ejaculation. As a glycoprotein with a chymotrypsin-like fold, KLK3 exhibits tryptic specificity, preferring basic residues like arginine at the P1 position, and is regulated by factors such as zinc inhibition and autolytic cleavage within its flexible 99-loop. In disease contexts, elevated circulating PSA levels serve as a key biomarker for prostate cancer detection and progression monitoring, though its specificity is limited by elevations in benign prostatic conditions. Structurally, KLK3 shares features with other classical kallikreins (KLK1-3), including an extended kallikrein loop influencing substrate access and activity. While no approved drugs directly target KLK3, structural studies support potential inhibitor development for prostate cancer therapeutics, addressing challenges like conformational dynamics and regulatory loops.

Other names

Prostate-specific antigenPSAKallikrein 3Semenogelase

Inhibition of proteolytic activity via active site binding (e.g., benzamidine, PPACK in structural analogs); zinc-mediated reversible inhibition; prevention of autolytic cleavage