Functional Study of Streptokinase Mutants
碩士 === 國立成功大學 === 生物化學研究所 === 85 === Streptokinase(SK) is an exoprotein of b-hemolytic streptococcus and is efficient as activator of plasminogen. SK is widely used as a thrombolytic agent in treatment of myocardial infarction. Adm...
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ndltd-TW-085NCKU01070102015-10-13T12:15:18Z http://ndltd.ncl.edu.tw/handle/02838848545815335999 Functional Study of Streptokinase Mutants 鏈激脢突變種的功能研究 Ou, Chung-pei 歐昌沛 碩士 國立成功大學 生物化學研究所 85 Streptokinase(SK) is an exoprotein of b-hemolytic streptococcus and is efficient as activator of plasminogen. SK is widely used as a thrombolytic agent in treatment of myocardial infarction. Administration of SK results in generation of plasmin in vascular system. By the action of plasmin, SK resolves clot indirectly. The mechanism whereby SK activates HPlg(human Plg) is not well studied yet. For developing new thrombolytic agent, SK variants were constructed and assayed. The sensitiveness of Lys59-Ser60 bond to the hydrolysis by plasmin has been reported(Shi et al, 1994), and the activity of the truncated SK molecule decreased. Two SK mutants, SKA59 & SKG59, were cloned. The lytic activity of mutants, both in casein and hole blood clot , was better than wildtype SK. It infers that the replacement of Plm sensitive sequence can prolong the activity of SK. Three variants, SKA48,51,53, SKA92,95,96 & SKA111,112,115, were used to probe function of the NH2 terminal in the activation mechanism. The average kinetic parameter, kplg/Kplg, is about 20% of the original, and activation activity were 30% or less of that of native SK. When mixed at 1:1 molar ratio, out of expectation, the variants quickly convert Plg to Plm(less than 1min). A model was proposed that SKA48,51,53, SKA92,95,96may have defect in substrate Plg activation and SKA111,112,115 may promote the transition state complex formation in activation of Plg moiety of SK-Plg complex。 Wu Hua-Lin 吳華林 1997 學位論文 ; thesis 83 zh-TW |
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碩士 === 國立成功大學 === 生物化學研究所 === 85 === Streptokinase(SK) is an exoprotein of b-hemolytic
streptococcus and is efficient as activator of plasminogen. SK
is widely used as a thrombolytic agent in treatment of
myocardial infarction. Administration of SK results in
generation of plasmin in vascular system. By the action of
plasmin, SK resolves clot indirectly. The mechanism whereby SK
activates HPlg(human Plg) is not well studied yet. For
developing new thrombolytic agent, SK variants were constructed
and assayed. The sensitiveness of Lys59-Ser60 bond to the
hydrolysis by plasmin has been reported(Shi et al, 1994), and
the activity of the truncated SK molecule decreased. Two SK
mutants, SKA59 & SKG59, were cloned. The lytic activity of
mutants, both in casein and hole blood clot , was better than
wildtype SK. It infers that the replacement of Plm sensitive
sequence can prolong the activity of SK. Three variants,
SKA48,51,53, SKA92,95,96 & SKA111,112,115, were used to probe
function of the NH2 terminal in the activation mechanism. The
average kinetic parameter, kplg/Kplg, is about 20% of the
original, and activation activity were 30% or less of that of
native SK. When mixed at 1:1 molar ratio, out of expectation,
the variants quickly convert Plg to Plm(less than 1min). A
model was proposed that SKA48,51,53, SKA92,95,96may have defect
in substrate Plg activation and SKA111,112,115 may promote the
transition state complex formation in activation of Plg moiety
of SK-Plg complex。
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author2 |
Wu Hua-Lin |
author_facet |
Wu Hua-Lin Ou, Chung-pei 歐昌沛 |
author |
Ou, Chung-pei 歐昌沛 |
spellingShingle |
Ou, Chung-pei 歐昌沛 Functional Study of Streptokinase Mutants |
author_sort |
Ou, Chung-pei |
title |
Functional Study of Streptokinase Mutants |
title_short |
Functional Study of Streptokinase Mutants |
title_full |
Functional Study of Streptokinase Mutants |
title_fullStr |
Functional Study of Streptokinase Mutants |
title_full_unstemmed |
Functional Study of Streptokinase Mutants |
title_sort |
functional study of streptokinase mutants |
publishDate |
1997 |
url |
http://ndltd.ncl.edu.tw/handle/02838848545815335999 |
work_keys_str_mv |
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