Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate specific antigen (PSA, also known as human kallikrein 3) is an important diagnostic indicator of prostatic disease. PSA exhibits low protease activity (>10(4)-fold less than chymotrypsin) under the usual in vitro assay conditions. In addition, PSA does not react readily with prototypical serine protease inactivators. We expressed human PSA (rh-PSA) in Escherichia coli and have demonstrated that rh-PSA has properties similar to those of native PSA isolated from human seminal fluid. Both PSA and rh-PSA are >10(3)-fold more active in the presence of 1.3 M Na(2)SO(4). This activation is anion-dependent, following the Hofmeister series when normality is considered: SO(4)(2)(-) approximately citrate > Ac(-) > Cl(-) > Br(-) > I(-). The nature of the cation has little effect on salt activation. The rate of inactivation of rh-PSA by DFP is 30-fold faster in the presence of 0.9 M Na(2)SO(4), and the rate of inactivation by Suc-Ala-Ala-Pro-Phe-CK is >20-fold faster under these conditions. Azapeptides containing Phe or Tyr at position P(1) also inactivate rh-PSA in the presence of high salt concentrations. These compounds represent the first described inhibitors designed to utilize the substrate binding subsites of PSA. CD spectroscopy demonstrates that the conformation of rh-PSA changes in the presence of high salt concentrations. Analytical ultracentifugation and dynamic light scattering indicate that PSA remains monomeric under high-salt conditions. Interestingly, human prostatic fluid contains as much as 150 micro mol citrate/g wet weight, which suggests that salt concentrations may regulate PSA activity in vivo.
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PMID:Modulation of recombinant human prostate-specific antigen: activation by Hofmeister salts and inhibition by azapeptides. Appendix: thermodynamic interpretation of the activation by concentrated salts. 1157 Aug 74

PSA complexed with alpha-1-anti-chymotrypsin (cPSA trade mark ) is the moiety in greatest proportion in the serum of men with prostate cancer (CAP). The performance of this analyte has been established primarily in retrospective archival serum. Studies indicate cPSA trade mark provides the specificity enhancement of the free-to-total PSA ratio, yet obviates the need to measure two markers. In the present investigation we sought to establish the stability of cPSA trade mark with long-term storage. Serum from men undergoing ultrasound-guided biopsy was utilized. Serum was assayed soon after collection and 18 months later. All serum was initially aliquotted and stored at -80 degrees C. There was no freeze-thaw. cPSA trade mark was measured utilizing the Bayer Immuno 1 method according to manufacturer's recommendations. The mean (s.d.) PSA was 5.5 (3.8) and 5.6 (3.9) ng/ml at the initial and subsequent testing, respectively. The medians were 4.3 and 4.4 ng/ml, respectively. No significant differences exist between the two determinants (r(2)=1.0, slope=1.01, t-test P=0.9194). These data establish for the first time the long-term stability of cPSA trade mark. Retrospective studies performed on archival material should give meaningful results. Prostate Cancer and Prostatic Diseases (2000) 3, 191-194
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PMID:Long-term stability of alpha-1-antichymotrypsin complexed form of prostate specific antigen. 1249 96