Article (Scientific journals)
Unraveling the structure and function of CdcPDE: A novel phosphodiesterase from Crotalus durissus collilineatus snake venom.
Oliveira, Isadora Sousa De; Pucca, Manuela Berto; Wiezel, Gisele Adriano et al.
2021In International Journal of Biological Macromolecules, 178, p. 180-192
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Keywords :
Animals; Cells, Cultured; Crotalid Venoms/chemistry; Crotalus; Humans; Keratinocytes/drug effects; Kinetics; Phosphoric Diester Hydrolases/chemistry/isolation & purification/toxicity; Substrate Specificity; Crotalus durissus collilineatus; Cytotoxicity; Phosphodiesterase
Abstract :
[en] This study reports the isolation, structural, biochemical, and functional characterization of a novel phosphodiesterase from Crotalus durissus collilineatus venom (CdcPDE). CdcPDE was successfully isolated from whole venom using three chromatographic steps and represented 0.7% of total protein content. CdcPDE was inhibited by EDTA and reducing agents, demonstrating that metal ions and disulfide bonds are necessary for its enzymatic activity. The highest enzymatic activity was observed at pH 8-8.5 and 37 °C. Kinetic parameters indicated a higher affinity for the substrate bis(p-nitrophenyl) phosphate compared to others snake venom PDEs. Its structural characterization was done by the determination of the protein primary sequence by Edman degradation and mass spectrometry, and completed by the building of molecular and docking-based models. Functional in vitro assays showed that CdcPDE is capable of inhibiting platelet aggregation induced by adenosine diphosphate in a dose-dependent manner and demonstrated that CdcPDE is cytotoxic to human keratinocytes. CdcPDE was recognized by the crotalid antivenom produced by the Instituto Butantan. These findings demonstrate that the study of snake venom toxins can reveal new molecules that may be relevant in cases of snakebite envenoming, and that can be used as molecular tools to study pathophysiological processes due to their specific biological activities.
Disciplines :
Chemistry
Author, co-author :
Oliveira, Isadora Sousa De
Pucca, Manuela Berto
Wiezel, Gisele Adriano
Cardoso, Iara Aimê
Bordon, Karla De Castro Figueiredo
Sartim, Marco Aurélio
Kalogeropoulos, Konstantinos
Ahmadi, Shirin
Baiwir, Dominique  ;  Université de Liège - ULiège > GIGA Platforms
Nonato, Maria Cristina
Sampaio, Suely Vilela
Laustsen, Andreas Hougaard
Auf dem Keller, Ulrich
Quinton, Loïc  ;  Université de Liège - ULiège > Département de chimie (sciences) > Chimie biologique
Arantes, Eliane Candiani
More authors (5 more) Less
Language :
English
Title :
Unraveling the structure and function of CdcPDE: A novel phosphodiesterase from Crotalus durissus collilineatus snake venom.
Publication date :
2021
Journal title :
International Journal of Biological Macromolecules
ISSN :
0141-8130
eISSN :
1879-0003
Publisher :
Elsevier, Netherlands
Volume :
178
Pages :
180-192
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright © 2021 Elsevier B.V. All rights reserved.
Available on ORBi :
since 25 August 2021

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