Structure, function, and regulation of the enzyme activity of prostate-specific antigen.

Abstract

Prostate-specific antigen (PSA) and human glandular kallikrein 1 (hGK-1) are structurally similar products of the human glandular kallikrein gene locus on chromosome 19 that become selectively expressed by human prostate tissue. PSA is one of the most abundant prostate-derived proteins in the seminal fluid. The mature form of PSA, a single-chain glycoprotein of 237 amino acids, is a serine protease manifesting restricted chymotrypsin-like activity. PSA is mainly responsible for gel dissolution in freshly ejaculated semen by proteolysis of the major gel-forming proteins semenogelin I and II and fibronectin. PSA complexed to alpha 1-antichymotrypsin (ACT) is the predominant molecular form of serum PSA, although complex formation is slow between the purified proteins in vitro. PSA also forms stable complexes with alpha 2-macroglobulin (alpha 2M) in vitro, but as this results in encapsulation of PSA and complete loss of the PSA epitopes, the in vivo significance of this complex formation is presently unclear. A free, noncomplexed form of PSA constitutes a minor fraction of the serum PSA, although serum ACT occurs at large molar excess.