Role of the peptide bond between $Lys^{59}$and $Ser^{60}$ of streptokinase in plasminogen activation = 플라스미노겐 활성화에 있어서 스트렙토키나제 $Ly^{59}$ $Ser^{60}$ 사이 펩티드결합의 역할

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Streptokinase(SK) is an extracellular protein produced by many strains of hemolytic streptococci, which lyses blood clots by activating plasminogen to plasmin. The complex of SK and human plasminogen is the functional activator that converts plasminogen to plasmin. It was reported that peptide bond at $Lys^{59}-Ser^{60}$, Lys^{387}-Asp^{388}$ and $Lys^{333}-Ala^{334}$ of streptokinase were cleaved when streptokinase forms complex with plasminogen. The 36-KDa peptide ($Ser^{60}-Lys^{387}$) shows 1/6 plasminogen activation activity of native streptokinase. However, when this 36-KDa peptide was preincubated with N-terminal peptide ($Ile^1-Lys^{59}$), this mixture shows plasminogen activation activity near the native streptokinase.In this study. the 59th residue Lys of streptokinase was mutated to Ala,Gln and Glu for the elucidation whether the cleavage of the peptide bond at $Lys^{59}-Ser^{60}$ was essential for the activation activity. Inferring from the unreduced SDS-PAGE, K59E and K59Q mutant showed similar cleavage pattern to wild type streptokinase. However,K59A mutant wasn``t cleaved. From the specificity of plasmin, the site of cleavage of mutant proteins might be not the 59th residue. The specific activities of mutant proteins were all lower than wild type streptokinase. However, the faster the cleavage at the peptide bond near $Lys^{59}$, the higher the plasminogen activation activity of mutated streptokinase. From these results, it is possible that the cleavage of the peptide bond at $Lys^{59}-Ser^{60}$ of streptokinase is required for the full plasminogen activation activity to some extent.
Advisors
Yang, Kyu-HwanByun, Si-Myung양규환변시명
Description
한국과학기술원 : 생물과학과,
Publisher
한국과학기술원
Issue Date
1996
Identifier
105877/325007 / 000943415
Language
eng
Description

학위논문(석사) - 한국과학기술원 : 생물과학과, 1996.2, [ v, 54 p. ]

Keywords

Plasminogen Activation; Site-Directed Mutagenesis; 스트렙토키나제; 플라스미노겐 활성화; Streptokinase; 특정부위돌연변이

URI
http://hdl.handle.net/10203/28501
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=105877&flag=dissertation
Appears in Collection
BS-Theses_Master(석사논문)
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