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Related Experiment Videos

Substrate specificity of prostate-specific antigen (PSA)

G S Coombs1, R C Bergstrom, J L Pellequer

  • 1Corvas International, Department of Molecular Biology, San Diego, CA 92121, USA.

Chemistry & Biology
|September 30, 1998
PubMed
Summary
This summary is machine-generated.

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Prostate-specific antigen (PSA) cleavage sites were identified using substrate phage display and iterative optimization. These findings reveal preferred substrate sequences for PSA, aiding in the development of improved diagnostic assays and inhibitors.

Area of Science:

  • Biochemistry
  • Enzymology

Background:

  • Prostate-specific antigen (PSA) is a key biomarker for prostate cancer.
  • PSA, a serine protease, exhibits chymotrypsin-like specificity.
  • Understanding PSA cleavage is crucial for developing targeted therapies.

Purpose of the Study:

  • To identify novel, labile substrate sequences for PSA cleavage.
  • To investigate the role of substrate subsites in PSA specificity and efficiency.

Main Methods:

  • Employed substrate phage display to screen for PSA cleavage sites.
  • Utilized iterative optimization of natural cleavage sites.
  • Quantified catalytic efficiencies of PSA cleavage.

Main Results:

  • Identified preferred PSA cleavage sequences: SS(Y/F)Y decreases S(G/S).

Related Experiment Videos

  • Achieved high catalytic efficiencies (2200-3100 M-1 s-1) with identified sequences.
  • Demonstrated the critical role of secondary subsites in defining substrate recognition.

    • Conclusions:

    • PSA recognition involves an extended binding site, influenced by secondary subsites.
    • Elucidated preferred subsite occupancy refines PSA structural models.
    • Facilitates development of sensitive activity-based assays and potent inhibitors for PSA.