Origins of the specificity of tissue-type plasminogen activator

Li Ding, Gary S. Coombs, Leif Strandberg, Marc Navre, David R. Corey, Edwin L. Madison

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

The role of subsite interactions in defining the stringent substrate specificity of tissue-type plasminogen activator (t-PA) has been examined by using an fd phage library that displayed random hexapeptide sequences and contained 2 x 108 independent recombinants. Forty-four individual hexapeptides were isolated and identified as improved substrates for t-PA. A peptide containing one of the selected amino acid sequences was cleaved by t- PA 5300 times more efficiently than a peptide that contained the primary sequence of the actual cleavage site in plasminogen. These results suggest that small peptides can mimic determinants that mediate specific proteolysis, emphasize the importance of subsite interactions in determining protease specificity, and have important implications for the evolution of protease cascades.

Original languageEnglish (US)
Pages (from-to)7627-7631
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number17
DOIs
StatePublished - Aug 15 1995

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Tissue Plasminogen Activator
Peptides
Peptide Hydrolases
Bacteriophage M13
Plasminogen Activators
Plasminogen
Substrate Specificity
Proteolysis
Amino Acid Sequence

ASJC Scopus subject areas

  • Genetics
  • General

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Origins of the specificity of tissue-type plasminogen activator. / Ding, Li; Coombs, Gary S.; Strandberg, Leif; Navre, Marc; Corey, David R.; Madison, Edwin L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 17, 15.08.1995, p. 7627-7631.

Research output: Contribution to journalArticle

Ding, Li ; Coombs, Gary S. ; Strandberg, Leif ; Navre, Marc ; Corey, David R. ; Madison, Edwin L. / Origins of the specificity of tissue-type plasminogen activator. In: Proceedings of the National Academy of Sciences of the United States of America. 1995 ; Vol. 92, No. 17. pp. 7627-7631.
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