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Structure and function of microplasminogen: II. Determinants of activation by urokinase and by the bacterial activator streptokinase
Author(s) -
Wang Jieyi,
Reich E.
Publication year - 1995
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560040912
Subject(s) - zymogen , streptokinase , active site , urokinase , activator (genetics) , disulfide bond , chemistry , plasminogen activator , stereochemistry , biochemistry , biophysics , structure–activity relationship , protein structure , microbiology and biotechnology , biology , enzyme , genetics , receptor , psychiatry , myocardial infarction , in vitro , psychology
We have used a group of human microplasminogens ( mPlg ), modified by residue substitutions, insertions, deletions, and chain breaks (1) to study the determinants of productive interactions with two plasminogen activators, urokinase ( uPA ), and streptokinase ( SK ); (2) to explore the basis of species specificity in the zymogen‐SK complex activity; and (3) to compare active SK complex formation in mPlg and microplasmin ( mPlm ). Modifications within the disulfide‐bonded loop containing the activation site and the adjacent hexadecapeptide upstream sequence showed that uPA recognition elements encompassed R 29 at the activation site and multiple elements extending upstream to perhaps 13 residues, all maintained in specific conformational register by the surrounding pairs of disulfide bonds. A generally parallel pattern of structural requirements was observed for active zymogen‐SK complex formation. Changes within the loop downstream of the activation site were tolerated well by uPA and poorly by SK . The introduction of selected short bovine ( Pig ) sequences in human mPlg reduced the activity of the resulting SK complexes. The requirements for active SK complex formation are different for mPlg and mPlm .