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

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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 α1‐antichymotrypsin, α2‐macroglobulin, and the α2‐macroglobulin‐analogue pregnancy zone protein. PSA formed inhibitory complexes with α1‐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 α1‐antichymotrypsin. The formation of stable complexes between PSA and α1‐antichymotrypsin occurred at a much slower rate than that between chymotrypsin and α1‐antichymotrypsin, and at a similar or slightly slower rate than that between PSA and α2‐macroglobulin. When added to normal blood plasma in vitro, active PSA formed stable complexes both with α2‐macroglobulin and α1‐antichymotrypsin. This complex formation may be a crucial determinant of the turnover of active PSA in intercellular fluid or blood plasma in vivo.