Structural model of human PSA: a target for prostate cancer therapy.

Based on unique biology of prostate cancer, prostate-specific antigen could be a useful target for prostate cancer therapies. Such targeting requires the identification of highly selective inhibitor-binding sites. Three-dimensional structure was calculated by homology modeling. The overall structure of human prostate-specific antigen is composed of two beta-barrel domain, kallikrein loop and active-site triad His57, Asp102, and Ser195. Structure of human prostate-specific antigen is quite similar to hK-1 and HPK-3. The major differences were observed at kallikrein loop and position of active site. The substrate-binding pocket is predominated by hydrophobic residues and the bottom of the specificity pocket contains Ser189 as in chymotrypsin, which provides substrate specificity. The hydrophobic, and preferentially aromatic (Trp215), amino acid residues are determinant of substrate binding due to the presence of hydrophobic crevice between Tyr99 and Trp215. Crystal structure of human prostate-specific antigen is not determined till now and hence the report on an accurate and comparative model of human prostate-specific antigen is probably to help in understanding their functional network and finally could be helpful in structure-based rational drug designing.