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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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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. |
format | Online Article Text |
id | pubmed-6609762 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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