Fibrinogen-clotting enzyme, pictobin, from Bothrops pictus snake venom. Structural and functional characterization

Dan E. Vivas-Ruiz, Gustavo A. Sandoval, Edgar Gonzalez-Kozlova, Jacquelyne Zarria-Romero, Fanny Lazo, Edith Rodríguez, Henrique P.B. Magalhães, Carlos Chávez-Olortegui, Luciana S. Oliveira, Valeria G. Alvarenga, Félix A. Urra, Jorge Toledo, Armando Yarlequé, Johannes A. Eble, Eladio F. Sanchez

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

1 Cita (Scopus)

Resumen

A thrombin-like enzyme, pictobin, was purified from Bothrops pictus snake venom. It is a 41-kDa monomeric glycoprotein as showed by mass spectrometry and contains approx. 45% carbohydrate by mass which could be removed with N-glycosidase. Pictobin coagulates plasma and fibrinogen, releasing fibrinopeptide A and induces the formation of a friable/porous fibrin network as visualized by SEM. The enzyme promoted platelet aggregation in human PRP and defibrination in mouse model and showed catalytic activity on chromogenic substrates S-2266, S-2366, S-2160 and S-2238. Pictobin interacts with the plasma inhibitor α2-macroglobulin, which blocks its interaction with fibrinogen but not with the small substrate BApNA. Heparin does not affect its enzymatic activity. Pictobin cross reacted with polyvalent bothropic antivenom, and its deglycosylated form reduced its catalytic action and antivenom reaction. In breast and lung cancer cells, pictobin inhibits the fibronectin-stimulated migration. Moreover, it produces strong NADH oxidation, mitochondrial depolarization, ATP decrease and fragmentation of mitochondrial network. These results suggest by first time that a snake venom serinprotease produces mitochondrial dysfunction by affecting mitochondrial dynamics and bioenergetics. Structural model of pictobin reveals a conserved chymotrypsin fold β/β hydrolase. These data indicate that pictobin has therapeutic potential in the treatment of cardiovascular disorders and metastatic disease.

Idioma originalInglés
Páginas (desde-hasta)779-795
Número de páginas17
PublicaciónInternational Journal of Biological Macromolecules
Volumen153
DOI
EstadoPublicada - 15 jun 2020

Nota bibliográfica

Publisher Copyright:
© 2020 Elsevier B.V.

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

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