Converting tissue plasminogen activator to a zymogen: A regulatory triad of Asp-His-Ser

Edwin L. Madison, Andreja Kobe, Mary Jane Gething, Joseph F. Sambrook, Elizabeth J. Goldsmith

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Unlike most serine proteases of the chymotrypsin family, tissue-type plasminogen activator (tPA) is secreted from cells as an active, single-chain enzyme with a catalytic efficiency only slightly lower than that of the proteolytically cleaved form. A zymogenic mutant of tPA has been engineered that displays a reduction in catalytic efficiency by a factor of 141 in the single-chain form while retaining full activity in the cleaved form. The residues introduced in the mutant, serine 292 and histidine 305, are proposed to form a hydrogen-bonded network with aspartate 477, similar to the aspartate 194-histidine 40-serine 32 network found to stabilize the zymogen chymotrypsinogen.

Original languageEnglish (US)
Pages (from-to)419-421
Number of pages3
JournalScience
Volume262
Issue number5132
DOIs
StatePublished - Jan 1 1993

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