Distinguishing the specificities of closely related proteases

E. L. Madison, S. H. Ke, G. S. Coombs, D. R. Corey, M. Navre

Research output: Contribution to journalArticle

Abstract

Elucidating subtle specificity differences between closely related enzymes is a fundamental challenge for both enzymology and drug design. We have addressed this issue for two closely related serine proteases, tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). Although these two proteases possess an extremely high degree of structural similarity, recognize the same primary endogenous substrate, and share common, physiological inhibitors, we have identified small, highly selective substrates whose relative reactivities towards the two enzymes vary by a factor of more than 9000. Discovery of selective substrates establishes a basis for the rational design of specific, small molecule inhibitors of each enzyme and provides new insight into details of molecular recognition by proteins.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number9
StatePublished - 1997

Fingerprint

Peptide Hydrolases
proteinases
enzymology
u-plasminogen activator
plasminogen activator
enzyme inhibitors
Drug Design
Urokinase-Type Plasminogen Activator
Serine Proteases
Enzyme Inhibitors
Tissue Plasminogen Activator
serine proteinases
Substrates
Enzymes
enzymes
Molecular recognition
drugs
Proteins
Molecules
proteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Madison, E. L., Ke, S. H., Coombs, G. S., Corey, D. R., & Navre, M. (1997). Distinguishing the specificities of closely related proteases. FASEB Journal, 11(9).

Distinguishing the specificities of closely related proteases. / Madison, E. L.; Ke, S. H.; Coombs, G. S.; Corey, D. R.; Navre, M.

In: FASEB Journal, Vol. 11, No. 9, 1997.

Research output: Contribution to journalArticle

Madison, EL, Ke, SH, Coombs, GS, Corey, DR & Navre, M 1997, 'Distinguishing the specificities of closely related proteases', FASEB Journal, vol. 11, no. 9.
Madison, E. L. ; Ke, S. H. ; Coombs, G. S. ; Corey, D. R. ; Navre, M. / Distinguishing the specificities of closely related proteases. In: FASEB Journal. 1997 ; Vol. 11, No. 9.
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