Enzymatic activity of prostate‐specific antigen and its reactions with extracellular serine proteinase inhibitors

Abstract

Prostate‐specific antigen (PSA) is one of the three most abundant prostatic‐secreted proteins in human semen. It is a serine proteinase that, in its primary structure, manifests extensive similarities with that of the Arg‐restricted glandular kallikrein‐like proteinases. When isolated from semen by the addition of chromatography on aprotinin‐Sepharose to a previously described procedure, PSA displayed chymotrypsin‐like activity and cleaved semenogelin and the semenogelin‐related proteins in a rapid and characteristic pattern, but had no trypsin‐like activity. About one third of the purified protein was found to be enzymatically inactive, due to cleavage carboxy‐terminal of Lys145. Active PSA formed SDS‐stable complexes with α 1‐antichymotrypsin, α 2‐macroglobulin, and the α 2‐macroglobulin‐analogue pregnancy zone protein. PSA formed inhibitory complexes with α 1‐antichymotrypsin at a molar ratio of 1:1, a reaction in which PSA cleaved the inhibitor in a position identical to that reported from the reaction between chymotrypsin and α 1‐antichymotrypsin. The formation of stable complexes between PSA and α 1‐antichymotrypsin occurred at a much slower rate than that between chymotrypsin and α 1‐antichymotrypsin, and at a similar or slightly slower rate than that between PSA and α 2‐macroglobulin. When added to normal blood plasma in vitro, active PSA formed stable complexes both with α 2‐macroglobulin and α 1‐antichymotrypsin. This complex formation may be a crucial determinant of the turnover of active PSA in intercellular fluid or blood plasma in vivo.