Antiplatelet mechanism of a subtilisin-like serine protease from Solanum tuberosum (StSBTc-3)

Autores
Pepe, Alfonso; Tito, Florencia Rocio; Guevara, Maria Gabriela
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The aims of this study are to characterize the antiplatelet activity of StSBTc-3, a potato serine protease with fibrino (geno) lytic activity, and to provide information on its mechanism of action. The results obtained show that StSBTc-3 inhibits clot retraction and prevents platelet aggregation induced by thrombin, convulxin, and A23187. Platelet aggregation inhibition occurs in a dose-dependent manner and is not affected by inactivation of StSBTc-3 with the inhibitor of serine proteases phenylmethylsulfonyl fluoride (PMSF). In addition, StSBTc-3 reduces fibrinogen binding onto platelets. In-silico calculations show a high binding affinity between StSBTc-3 and human α2bβ3 integrin suggesting that the antiplatelet activity of StSBTc-3 could be associated with the fibronectin type III domain present in its amino acid sequence. Binding experiments show that StSBTc-3 binds to α2bβ3 preventing the interaction between α2bβ3 and fibrinogen and, consequently, inhibiting platelet aggregation. StSBTc-3 represents a promising compound to be considered as an alternative to commercially available drugs used in cardiovascular therapies.
Fil: Pepe, Alfonso. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina. University of Florida; Estados Unidos
Fil: Tito, Florencia Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina
Fil: Guevara, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina
Materia
FIBRONECTIN DOMAIN
HEMOSTASIS
PLATELET AGGREGATION
SERINE PROTEASES
Nivel de accesibilidad
acceso embargado
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/219052

id CONICETDig_33290c2ba626200c480e48ac6fe4d6a6
oai_identifier_str oai:ri.conicet.gov.ar:11336/219052
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Antiplatelet mechanism of a subtilisin-like serine protease from Solanum tuberosum (StSBTc-3)Pepe, AlfonsoTito, Florencia RocioGuevara, Maria GabrielaFIBRONECTIN DOMAINHEMOSTASISPLATELET AGGREGATIONSERINE PROTEASEShttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3The aims of this study are to characterize the antiplatelet activity of StSBTc-3, a potato serine protease with fibrino (geno) lytic activity, and to provide information on its mechanism of action. The results obtained show that StSBTc-3 inhibits clot retraction and prevents platelet aggregation induced by thrombin, convulxin, and A23187. Platelet aggregation inhibition occurs in a dose-dependent manner and is not affected by inactivation of StSBTc-3 with the inhibitor of serine proteases phenylmethylsulfonyl fluoride (PMSF). In addition, StSBTc-3 reduces fibrinogen binding onto platelets. In-silico calculations show a high binding affinity between StSBTc-3 and human α2bβ3 integrin suggesting that the antiplatelet activity of StSBTc-3 could be associated with the fibronectin type III domain present in its amino acid sequence. Binding experiments show that StSBTc-3 binds to α2bβ3 preventing the interaction between α2bβ3 and fibrinogen and, consequently, inhibiting platelet aggregation. StSBTc-3 represents a promising compound to be considered as an alternative to commercially available drugs used in cardiovascular therapies.Fil: Pepe, Alfonso. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina. University of Florida; Estados UnidosFil: Tito, Florencia Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Guevara, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaElsevier France-Editions Scientifiques Medicales Elsevier2023-09info:eu-repo/date/embargoEnd/2024-09-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/219052Pepe, Alfonso; Tito, Florencia Rocio; Guevara, Maria Gabriela; Antiplatelet mechanism of a subtilisin-like serine protease from Solanum tuberosum (StSBTc-3); Elsevier France-Editions Scientifiques Medicales Elsevier; Biochimie; 218; 9-2023; 152-1610300-9084CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0300908423002389info:eu-repo/semantics/altIdentifier/doi/10.1016/j.biochi.2023.09.011info:eu-repo/semantics/embargoedAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:17Zoai:ri.conicet.gov.ar:11336/219052instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:11:17.76CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Antiplatelet mechanism of a subtilisin-like serine protease from Solanum tuberosum (StSBTc-3)
title Antiplatelet mechanism of a subtilisin-like serine protease from Solanum tuberosum (StSBTc-3)
spellingShingle Antiplatelet mechanism of a subtilisin-like serine protease from Solanum tuberosum (StSBTc-3)
Pepe, Alfonso
FIBRONECTIN DOMAIN
HEMOSTASIS
PLATELET AGGREGATION
SERINE PROTEASES
title_short Antiplatelet mechanism of a subtilisin-like serine protease from Solanum tuberosum (StSBTc-3)
title_full Antiplatelet mechanism of a subtilisin-like serine protease from Solanum tuberosum (StSBTc-3)
title_fullStr Antiplatelet mechanism of a subtilisin-like serine protease from Solanum tuberosum (StSBTc-3)
title_full_unstemmed Antiplatelet mechanism of a subtilisin-like serine protease from Solanum tuberosum (StSBTc-3)
title_sort Antiplatelet mechanism of a subtilisin-like serine protease from Solanum tuberosum (StSBTc-3)
dc.creator.none.fl_str_mv Pepe, Alfonso
Tito, Florencia Rocio
Guevara, Maria Gabriela
author Pepe, Alfonso
author_facet Pepe, Alfonso
Tito, Florencia Rocio
Guevara, Maria Gabriela
author_role author
author2 Tito, Florencia Rocio
Guevara, Maria Gabriela
author2_role author
author
dc.subject.none.fl_str_mv FIBRONECTIN DOMAIN
HEMOSTASIS
PLATELET AGGREGATION
SERINE PROTEASES
topic FIBRONECTIN DOMAIN
HEMOSTASIS
PLATELET AGGREGATION
SERINE PROTEASES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The aims of this study are to characterize the antiplatelet activity of StSBTc-3, a potato serine protease with fibrino (geno) lytic activity, and to provide information on its mechanism of action. The results obtained show that StSBTc-3 inhibits clot retraction and prevents platelet aggregation induced by thrombin, convulxin, and A23187. Platelet aggregation inhibition occurs in a dose-dependent manner and is not affected by inactivation of StSBTc-3 with the inhibitor of serine proteases phenylmethylsulfonyl fluoride (PMSF). In addition, StSBTc-3 reduces fibrinogen binding onto platelets. In-silico calculations show a high binding affinity between StSBTc-3 and human α2bβ3 integrin suggesting that the antiplatelet activity of StSBTc-3 could be associated with the fibronectin type III domain present in its amino acid sequence. Binding experiments show that StSBTc-3 binds to α2bβ3 preventing the interaction between α2bβ3 and fibrinogen and, consequently, inhibiting platelet aggregation. StSBTc-3 represents a promising compound to be considered as an alternative to commercially available drugs used in cardiovascular therapies.
Fil: Pepe, Alfonso. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina. University of Florida; Estados Unidos
Fil: Tito, Florencia Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina
Fil: Guevara, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina
description The aims of this study are to characterize the antiplatelet activity of StSBTc-3, a potato serine protease with fibrino (geno) lytic activity, and to provide information on its mechanism of action. The results obtained show that StSBTc-3 inhibits clot retraction and prevents platelet aggregation induced by thrombin, convulxin, and A23187. Platelet aggregation inhibition occurs in a dose-dependent manner and is not affected by inactivation of StSBTc-3 with the inhibitor of serine proteases phenylmethylsulfonyl fluoride (PMSF). In addition, StSBTc-3 reduces fibrinogen binding onto platelets. In-silico calculations show a high binding affinity between StSBTc-3 and human α2bβ3 integrin suggesting that the antiplatelet activity of StSBTc-3 could be associated with the fibronectin type III domain present in its amino acid sequence. Binding experiments show that StSBTc-3 binds to α2bβ3 preventing the interaction between α2bβ3 and fibrinogen and, consequently, inhibiting platelet aggregation. StSBTc-3 represents a promising compound to be considered as an alternative to commercially available drugs used in cardiovascular therapies.
publishDate 2023
dc.date.none.fl_str_mv 2023-09
info:eu-repo/date/embargoEnd/2024-09-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/219052
Pepe, Alfonso; Tito, Florencia Rocio; Guevara, Maria Gabriela; Antiplatelet mechanism of a subtilisin-like serine protease from Solanum tuberosum (StSBTc-3); Elsevier France-Editions Scientifiques Medicales Elsevier; Biochimie; 218; 9-2023; 152-161
0300-9084
CONICET Digital
CONICET
url http://hdl.handle.net/11336/219052
identifier_str_mv Pepe, Alfonso; Tito, Florencia Rocio; Guevara, Maria Gabriela; Antiplatelet mechanism of a subtilisin-like serine protease from Solanum tuberosum (StSBTc-3); Elsevier France-Editions Scientifiques Medicales Elsevier; Biochimie; 218; 9-2023; 152-161
0300-9084
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0300908423002389
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.biochi.2023.09.011
dc.rights.none.fl_str_mv info:eu-repo/semantics/embargoedAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv embargoedAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier France-Editions Scientifiques Medicales Elsevier
publisher.none.fl_str_mv Elsevier France-Editions Scientifiques Medicales Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842270152147599360
score 13.13397