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Registro Completo |
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Biblioteca(s): |
Embrapa Agricultura Digital. |
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Data corrente: |
23/06/2025 |
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Data da última atualização: |
23/06/2025 |
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Tipo da produção científica: |
Artigo em Periódico Indexado |
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Autoria: |
SANTOS, R. V. dos; BARRIONUEVO, M. V. F.; VIEIRA, M. R. F.; MAZONI, I.; TASIC, L. |
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Afiliação: |
RONEY VANDER DOS SANTOS, UNIVERSIDADE ESTADUAL DE CAMPINAS; MANOEL VICTOR FRUTUOSO BARRIONUEVO, UNIVERSIDADE ESTADUAL DE CAMPINAS; MIKAEL RANGEL FERNANDES VIEIRA, UNIVERSITY OF BUENOS AIRES; IVAN MAZONI, CNPTIA; LJUBICA TASIC, UNIVERSIDADE ESTADUAL DE CAMPINAS. |
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Título: |
Plasminogen activator inhibitors in thrombosis: structural analysis and potential natural inhibitors. |
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Ano de publicação: |
2025 |
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Fonte/Imprenta: |
ACS Omega, 2025. |
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DOI: |
http://doi.org/10.1021/acsomega.5c02926 |
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Idioma: |
Inglês |
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Notas: |
On-line first. |
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Conteúdo: |
ABSTRACT: Thrombosis, a critical pathological event characterized by excessive clot formation, is primarily regulated by the fibrinolytic system, where plasminogen activator inhibitors (PAIs) are pivotal. Among them, PAI-1 is the most relevant due to its strong inhibitory effect on fibrinolysis, contributing to various thrombotic disorders. In addition, PAI-2 and PAI-3 have been implicated in distinct physiological and pathological conditions. Understanding their structural and functional characteristics is essential for the development of targeted anticoagulant therapies. This study comprehensively analyzes the secondary and tertiary structures of PAI-1, PAI-2, and PAI-3, highlighting conserved domains and their roles in protein function. Comparative phylogenetic analysis confirms their evolutionary relationships, reinforcing their shared inhibitory mechanisms. Structural superimposition and root-mean-square deviation (RMSD) calculations demonstrate varying degrees of similarity among these inhibitors, with PAI-2 and PAI-3 being more closely related. Furthermore, molecular docking and molecular dynamics simulations were employed to identify natural product-derived inhibitors, focusing on tanshinones and phenolic acids extracted from Salvia miltiorrhiza. Among these compounds, salvianolic acid B and tanshinone IIA sulfate exhibited the highest binding affinity and stability, suggesting their potential as lead compounds for the development of novel fibrinolytic agents. Our findings contribute to understanding PAI structural dynamics and provide insights into natural inhibitor design, paving the way for innovative therapeutic strategies against thrombosis and related disorders. MenosABSTRACT: Thrombosis, a critical pathological event characterized by excessive clot formation, is primarily regulated by the fibrinolytic system, where plasminogen activator inhibitors (PAIs) are pivotal. Among them, PAI-1 is the most relevant due to its strong inhibitory effect on fibrinolysis, contributing to various thrombotic disorders. In addition, PAI-2 and PAI-3 have been implicated in distinct physiological and pathological conditions. Understanding their structural and functional characteristics is essential for the development of targeted anticoagulant therapies. This study comprehensively analyzes the secondary and tertiary structures of PAI-1, PAI-2, and PAI-3, highlighting conserved domains and their roles in protein function. Comparative phylogenetic analysis confirms their evolutionary relationships, reinforcing their shared inhibitory mechanisms. Structural superimposition and root-mean-square deviation (RMSD) calculations demonstrate varying degrees of similarity among these inhibitors, with PAI-2 and PAI-3 being more closely related. Furthermore, molecular docking and molecular dynamics simulations were employed to identify natural product-derived inhibitors, focusing on tanshinones and phenolic acids extracted from Salvia miltiorrhiza. Among these compounds, salvianolic acid B and tanshinone IIA sulfate exhibited the highest binding affinity and stability, suggesting their potential as lead compounds for the development of novel fibrinolytic agents. Our fi... Mostrar Tudo |
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Palavras-Chave: |
Análise estrutural; Inibidor do ativador do plasminogênio; Inibidores naturais; Natural inhibitors; Structural analysis; Trombose. |
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Thesaurus Nal: |
Thrombosis. |
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Categoria do assunto: |
X Pesquisa, Tecnologia e Engenharia |
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Marc: |
LEADER 02538naa a2200277 a 4500
001 2176714
005 2025-06-23
008 2025 bl uuuu u00u1 u #d
024 7 $ahttp://doi.org/10.1021/acsomega.5c02926$2DOI
100 1 $aSANTOS, R. V. dos
245 $aPlasminogen activator inhibitors in thrombosis$bstructural analysis and potential natural inhibitors.$h[electronic resource]
260 $c2025
500 $aOn-line first.
520 $aABSTRACT: Thrombosis, a critical pathological event characterized by excessive clot formation, is primarily regulated by the fibrinolytic system, where plasminogen activator inhibitors (PAIs) are pivotal. Among them, PAI-1 is the most relevant due to its strong inhibitory effect on fibrinolysis, contributing to various thrombotic disorders. In addition, PAI-2 and PAI-3 have been implicated in distinct physiological and pathological conditions. Understanding their structural and functional characteristics is essential for the development of targeted anticoagulant therapies. This study comprehensively analyzes the secondary and tertiary structures of PAI-1, PAI-2, and PAI-3, highlighting conserved domains and their roles in protein function. Comparative phylogenetic analysis confirms their evolutionary relationships, reinforcing their shared inhibitory mechanisms. Structural superimposition and root-mean-square deviation (RMSD) calculations demonstrate varying degrees of similarity among these inhibitors, with PAI-2 and PAI-3 being more closely related. Furthermore, molecular docking and molecular dynamics simulations were employed to identify natural product-derived inhibitors, focusing on tanshinones and phenolic acids extracted from Salvia miltiorrhiza. Among these compounds, salvianolic acid B and tanshinone IIA sulfate exhibited the highest binding affinity and stability, suggesting their potential as lead compounds for the development of novel fibrinolytic agents. Our findings contribute to understanding PAI structural dynamics and provide insights into natural inhibitor design, paving the way for innovative therapeutic strategies against thrombosis and related disorders.
650 $aThrombosis
653 $aAnálise estrutural
653 $aInibidor do ativador do plasminogênio
653 $aInibidores naturais
653 $aNatural inhibitors
653 $aStructural analysis
653 $aTrombose
700 1 $aBARRIONUEVO, M. V. F.
700 1 $aVIEIRA, M. R. F.
700 1 $aMAZONI, I.
700 1 $aTASIC, L.
773 $tACS Omega, 2025.
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Registro original: |
Embrapa Agricultura Digital (CNPTIA) |
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