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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...

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Autores principales: Rafipour, Maryam, Keramati, Malihe, Aslani, Mohammad Mehdi, Arashkia, Arash, Roohvand, Farzin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609762/
https://www.ncbi.nlm.nih.gov/pubmed/31087538
http://dx.doi.org/10.1002/2211-5463.12657
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author Rafipour, Maryam
Keramati, Malihe
Aslani, Mohammad Mehdi
Arashkia, Arash
Roohvand, Farzin
author_facet Rafipour, Maryam
Keramati, Malihe
Aslani, Mohammad Mehdi
Arashkia, Arash
Roohvand, Farzin
author_sort Rafipour, Maryam
collection PubMed
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 α(2)‐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.
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spelling pubmed-66097622019-07-16 The β‐domain of streptokinase affects several functionalities, including specific/proteolytic activity kinetics Rafipour, Maryam Keramati, Malihe Aslani, Mohammad Mehdi Arashkia, Arash Roohvand, Farzin FEBS Open Bio Research Articles 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 α(2)‐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. John Wiley and Sons Inc. 2019-05-30 /pmc/articles/PMC6609762/ /pubmed/31087538 http://dx.doi.org/10.1002/2211-5463.12657 Text en © 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Rafipour, Maryam
Keramati, Malihe
Aslani, Mohammad Mehdi
Arashkia, Arash
Roohvand, Farzin
The β‐domain of streptokinase affects several functionalities, including specific/proteolytic activity kinetics
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 Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609762/
https://www.ncbi.nlm.nih.gov/pubmed/31087538
http://dx.doi.org/10.1002/2211-5463.12657
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