Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519176 (PSA)
 5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human prostate specific antigen, PSA, is a product of the human glandular kallikrein gene locus on chromosome 19 that is almost selectively expressed by prostate tissue. PSA is one of the dominating prostate derived proteins in 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. In semen approximately two thirds of PSA is enzymatically active. The remaining 30-40% is inactive due to internal cleavage(s). A few per cent of PSA in semen is complexed to the protein C inhibitor. PSA complexed to alpha 1-antichymotrypsin (ACT) constitutes 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 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, non-complexed form of PSA constitutes a minor fraction of the serum PSA despite the large molar excess of antiproteasees such as ACT. In patients with carcinoma of the prostate the serum PSA level increases. Analysis of the serum level of PSA is used both for diagnosing and monitoring patients with carcinoma of the prostate (CAP).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemistry of prostate specific antigen, PSA. 754 81

In addition to kallikrein hK3, a serine protease generally reported as PSA (prostate-specific antigen), at least two other enzymes in human seminal plasma also cleave synthetic peptidyl substrates derived from the sequence of human semenogelins. We have identified one of these as prostatic acid phosphatase (PAP), a major component of prostatic fluid whose physiological function is unclear. The other is a high Mr basic protein present at low concentrations in seminal plasma and that remains to be characterized. PAP was purified to homogeneity from freshly ejaculated seminal plasma. Its N-terminal sequence and its phosphatase properties (hydrolysis of para-nitrophenylphosphate at low pH) were determined, and its inhibition by sodium fluoride measured. Both purified and commercial PAP also had amidolytic activity on peptide substrates derived from the semenogelin sequence at neutral and slightly basic pH. The k(cat)/K(m) values were in the 10(2)-10(3) m(-1) x s(-1) range using fluorogenic semenogelin-derived substrates whose peptidyl moiety included cleavage sites that had been identified ex vivo. PAP cleavage sites differed from those of hK3 and were mainly at P1 = Gln residues or between residues bearing hydroxyl groups. PAP amidolytic activity was poorly inhibited by all currently used wide spectrum proteinase inhibitors. Only 3-4 dichloroisocoumarin and benzamidine inhibited purified PAP. Purified human semenogelin was cleaved by purified and commercial PAP at neutral pH; the two main cleavage sites were at Tyr292 and Ser170 (semenogelin I sequence), only the former has been identified ex vivo by analysis of seminal plasma.
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PMID:Amidolytic activity of prostatic acid phosphatase on human semenogelins and semenogelin-derived synthetic substrates. 1178 34

Human prostate-specific antigen (PSA or KLK3) is an important marker for the diagnosis and management of prostate cancer. This is an androgen-regulated glycoprotein of the kallikrein-related protease family secreted by prostatic epithelial cells. Its physiological function is to cleave semenogelins in the seminal coagulum and its enzymatic activity is strongly modulated by zinc ions. Here we present the first crystal structure of human PSA in complex with monoclonal antibody (mAb) 8G8F5 that enhances its enzymatic activity. The mAb recognizes an epitope composed of five discontinuous segments including residues from the kallikrein loop and stabilizes PSA in an "open and active conformation" that accelerates catalysis. We also present the crystal structure of PSA in complex with both the mAb 8G8F5 and a fluorogenic substrate Mu-KGISSQY-AFC, derived from semenogelin I. By exploiting the inhibition of PSA by zinc ions, we were able to obtain a substrate acyl intermediate covalently linked to the catalytic serine, at pH 7.3 but not at pH 5.5. Moreover, the inhibition of PSA activity by zinc was found to be modulated by pH variations but not by the antibody binding. The correlation of the different data with the physiological conditions under which PSA can cleave semenogelins is discussed.
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PMID:Crystal structure of a ternary complex between human prostate-specific antigen, its substrate acyl intermediate and an activating antibody. 1818 50