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Enzymatic action of prostate-specific antigen (PSA or hK3): substrate specificity and regulation by Zn(2+), a tight-binding inhibitor.
- Source :
-
The Prostate [Prostate] 2000 Oct 01; Vol. 45 (2), pp. 132-9. - Publication Year :
- 2000
-
Abstract
- Background: In semen, prostate-specific antigen (PSA or hK3) digests the gel proteins semenogelin I and II, resulting in liquefaction and the release of motile spermatozoa. We characterized the substrate specificity and zinc-mediated inhibition of PSA.<br />Methods: The proteolysis of human semenogelin I (SgI) and II (SgII) by PSA was characterized by purification of generated SgI and SgII fragments, N-terminal sequencing, and mass spectrometry. Zn(2+)-inhibition of PSA was studied using a chromogenic substrate.<br />Results: Eighteen cleavage sites in SgI and 16 in SgII were identified. Cleavages were identified mainly as the C-terminal of certain tyrosine and glutamine residues, but also the C-terminal of histidine, aspartic acid, leucine, serine, and asparagine residues. No cleavages were identified at any arginine, lysine, phenylalanine, tryptophan, or methionine residues, indicating that the substrate specificity of PSA is distinct from that of trypsin, chymotrypsin, tissue kallkrein (hK1), and kallikrein 2 (hK2). Zn(2+) ions have a dramatic effect on PSA activity; the data indicate that Zn(2+) is a tight-binding inhibitor of PSA activity.<br />Conclusions: The data will enable the optimized design of PSA activity assays, which may prove instrumental to uncovering the role of PSA in cancer and reproduction. The inhibition data indicate that Zn(2+) could regulate PSA activity, which may prove important in the development of efficient inhibitors of PSA activity.<br /> (Copyright 2000 Wiley-Liss, Inc.)
- Subjects :
- Amino Acid Sequence
Cations, Divalent
Enzymes
Humans
Hydrolysis
Molecular Sequence Data
Prostate-Specific Antigen antagonists & inhibitors
Semen
Sequence Homology, Amino Acid
Substrate Specificity
alpha 1-Antichymotrypsin metabolism
Enzyme Inhibitors metabolism
Gonadal Steroid Hormones metabolism
Prostate-Specific Antigen metabolism
Seminal Plasma Proteins
Seminal Vesicle Secretory Proteins
Zinc metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0270-4137
- Volume :
- 45
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Prostate
- Publication Type :
- Academic Journal
- Accession number :
- 11027412
- Full Text :
- https://doi.org/10.1002/1097-0045(20001001)45:2<132::aid-pros7>3.0.co;2-3