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The ?-domain of streptokinase affects several functionalities, including specific/proteolytic activity kinetics.


ABSTRACT: Streptokinase (SK) is a plasminogen activator which converts inactive plasminogen (Pg) to active plasmin (Pm), which cleaves fibrin clots. SK secreted by groups A, C, and G Streptococcus (SKA/SKC/SKG) is composed of three domains: SK?, SK? and SK?. Previous domain-swapping studies between SK1/SK2b-cluster variants revealed that SK? plays a major role in the activation of human Pg. Here, we carried out domain-swapping between skcg-SK/SK2-cluster variants to determine the involvement of SK? in several SK functionalities, including specific/proteolytic activity kinetics, fibrinogen-bound Pg activation and ?2 -antiplasmin resistance. Our results indicate that SK? has a minor to determining role in these diverse functionalities for skcg-SK and SK2b variants, which might potentially be accompanied by few critical residues acting as hot spots. Our findings enhance our understanding of the roles of SK? and hot spots in different functional characteristics of SK clusters and may aid in the engineering of fibrin-specific variants of SK for breaking down blood clots with potentially higher efficacy and safety.

SUBMITTER: Rafipour M 

PROVIDER: S-EPMC6609762 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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The β-domain of streptokinase affects several functionalities, including specific/proteolytic activity kinetics.

Rafipour Maryam M   Keramati Malihe M   Aslani Mohammad Mehdi MM   Arashkia Arash A   Roohvand Farzin F  

FEBS open bio 20190530 7


Streptokinase (SK) is a plasminogen activator which converts inactive plasminogen (Pg) to active plasmin (Pm), which cleaves fibrin clots. SK secreted by groups A, C, and G Streptococcus (SKA/SKC/SKG) is composed of three domains: SKα, SKβ and SKγ. Previous domain-swapping studies between SK1/SK2b-cluster variants revealed that SKβ plays a major role in the activation of human Pg. Here, we carried out domain-swapping between skcg-SK/SK2-cluster variants to determine the involvement of SKβ in sev  ...[more]

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