The β‐domain of streptokinase affects several functionalities, including specific/proteolytic activity kinetics
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‐c...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-07-01
|
| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2211-5463.12657 |
| _version_ | 1797681636790239232 |
|---|---|
| author | Maryam Rafipour Malihe Keramati Mohammad Mehdi Aslani Arash Arashkia Farzin Roohvand |
| author_facet | Maryam Rafipour Malihe Keramati Mohammad Mehdi Aslani Arash Arashkia Farzin Roohvand |
| author_sort | Maryam Rafipour |
| collection | DOAJ |
| description | 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 several SK functionalities, including specific/proteolytic activity kinetics, fibrinogen‐bound Pg activation and α2‐antiplasmin resistance. Our results indicate that SKβ 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 SKβ 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. |
| first_indexed | 2024-03-11T23:47:44Z |
| format | Article |
| id | doaj.art-242b3dfc29f04d59818a9f18c5edac04 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-03-11T23:47:44Z |
| publishDate | 2019-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-242b3dfc29f04d59818a9f18c5edac042023-09-19T08:50:32ZengWileyFEBS Open Bio2211-54632019-07-01971259126910.1002/2211-5463.12657The β‐domain of streptokinase affects several functionalities, including specific/proteolytic activity kineticsMaryam Rafipour0Malihe Keramati1Mohammad Mehdi Aslani2Arash Arashkia3Farzin Roohvand4Virology Department Pasteur Institute of Iran Tehran IranNanoBiotechnology Department Pasteur Institute of Iran Tehran IranMicrobiology Department Pasteur Institute of Iran Tehran IranVirology Department Pasteur Institute of Iran Tehran IranVirology Department Pasteur Institute of Iran Tehran IranStreptokinase (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 several SK functionalities, including specific/proteolytic activity kinetics, fibrinogen‐bound Pg activation and α2‐antiplasmin resistance. Our results indicate that SKβ 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 SKβ 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.https://doi.org/10.1002/2211-5463.12657fibrinolysisplasminogen activationprotein domainsstreptococci clustersstreptokinaseα2‐antiplasmin resistance |
| spellingShingle | Maryam Rafipour Malihe Keramati Mohammad Mehdi Aslani Arash Arashkia Farzin Roohvand The β‐domain of streptokinase affects several functionalities, including specific/proteolytic activity kinetics FEBS Open Bio fibrinolysis plasminogen activation protein domains streptococci clusters streptokinase α2‐antiplasmin resistance |
| title | The β‐domain of streptokinase affects several functionalities, including specific/proteolytic activity kinetics |
| title_full | The β‐domain of streptokinase affects several functionalities, including specific/proteolytic activity kinetics |
| title_fullStr | The β‐domain of streptokinase affects several functionalities, including specific/proteolytic activity kinetics |
| title_full_unstemmed | The β‐domain of streptokinase affects several functionalities, including specific/proteolytic activity kinetics |
| title_short | The β‐domain of streptokinase affects several functionalities, including specific/proteolytic activity kinetics |
| title_sort | β domain of streptokinase affects several functionalities including specific proteolytic activity kinetics |
| topic | fibrinolysis plasminogen activation protein domains streptococci clusters streptokinase α2‐antiplasmin resistance |
| url | https://doi.org/10.1002/2211-5463.12657 |
| work_keys_str_mv | AT maryamrafipour thebdomainofstreptokinaseaffectsseveralfunctionalitiesincludingspecificproteolyticactivitykinetics AT malihekeramati thebdomainofstreptokinaseaffectsseveralfunctionalitiesincludingspecificproteolyticactivitykinetics AT mohammadmehdiaslani thebdomainofstreptokinaseaffectsseveralfunctionalitiesincludingspecificproteolyticactivitykinetics AT arasharashkia thebdomainofstreptokinaseaffectsseveralfunctionalitiesincludingspecificproteolyticactivitykinetics AT farzinroohvand thebdomainofstreptokinaseaffectsseveralfunctionalitiesincludingspecificproteolyticactivitykinetics AT maryamrafipour bdomainofstreptokinaseaffectsseveralfunctionalitiesincludingspecificproteolyticactivitykinetics AT malihekeramati bdomainofstreptokinaseaffectsseveralfunctionalitiesincludingspecificproteolyticactivitykinetics AT mohammadmehdiaslani bdomainofstreptokinaseaffectsseveralfunctionalitiesincludingspecificproteolyticactivitykinetics AT arasharashkia bdomainofstreptokinaseaffectsseveralfunctionalitiesincludingspecificproteolyticactivitykinetics AT farzinroohvand bdomainofstreptokinaseaffectsseveralfunctionalitiesincludingspecificproteolyticactivitykinetics |