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; Cardoso, Iara Aimê; Bordon, Karla de Castro Figueiredo; Sartim, Marco A.; Kalogeropoulos, Konstantinos; Ahmadi, Shirin; Baiwir, Dominique; Nonato, Maria Cristina; Sampaio, Suely Vilela; Laustsen, Andreas Hougaard; Keller, Ulrich auf dem; Quinton, Loïc; Arantes, Eliane Candiani

doi:10.1016/j.ijbiomac.2021.02.120

Cited by 10 publications

(7 citation statements)

References 84 publications

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“…The isolation and characterization of Cdc PDE was performed in our previous study, showing its low recovery (0.71%) [ 17 ]. Cdc PDE at 20 µg/mL (0.2 mM) exhibited significantly lower levels of cell-free-DNA in comparison with undigested groups ( Figure 2 ), indicating its ability of cell-free DNA degradation.…”

Section: Resultsmentioning

confidence: 99%

“…Others substrates were tested in PDEs studies to characterize their enzymatic activity, such as bis ( p -nitrophenyl) phosphate (0.4 mM [ 20 ], 1 mM [ 17 ] and 5 mM [ 21 ]), adenosine triphosphate (ATP, 0.05 mM), nicotinamide adenine dinucleotide (NAD, 0.05 mM), adenosine diphosphate (ADP, 0.05 mM), nicotinamide guanine dinucleotide (NGD, 0.05 mM), and adenosine monophosphate (AMP, 0.05 mM) [ 22 ], among others [ 18 , 19 ]. Although our study did not aim to characterize the enzymatic kinetics of Cdc PDE, using λDNA as substrate, we observed that the amount of substrate used in the cited studies is much higher than in our study (6 × 10 −13 mM), and even though the hydrolysis was observed.…”

Section: Resultsmentioning

confidence: 99%

“…Cdc PDE, a phosphodiesterase, was recently (2021) isolated from the Crotalus durissus collilineatus rattlesnake venom, and was completely characterized. Moreover, functional previous studies demonstrated that the Cdc PDE was able to inhibit ADP-induced platelet aggregation and to cause a cytotoxic effect to human keratinocytes [ 17 ]. Knowing that Cdc PDE is classified as a nuclease, able to degrade DNA (i.e., DNAse [ 18 , 19 ], this study aimed to verify if the rattlesnake-derived molecule could degrade cell-free DNA from NETs ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

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A Promising Biomolecule Able to Degrade Neutrophil Extracellular Traps: CdcPDE, a Rattlesnake Phosphodiesterase

Oliveira

Costa

Veras

et al. 2023

Toxins

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Neutrophil extracellular traps (NETs) are an important mechanism for defense against pathogens. Their overproduction can be harmful since excessive NET formation promotes inflammation and tissue damage in several diseases. Nucleases are capable to degrade NET on basis of their DNA hydrolysis activity, including the CdcPDE, a nuclease isolated from Crotalus durissus collilineatus snake venom. Here, we report a new finding about CdcPDE activity, demonstrating its efficiency in degrading cell-free DNA from NETs, being a potential candidate to assist in therapies targeting inflammatory diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Promising Biomolecule Able to Degrade Neutrophil Extracellular Traps: CdcPDE, a Rattlesnake Phosphodiesterase

Oliveira

Costa

Veras

et al. 2023

Toxins

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“…The assay was performed following methodology from Oliveira et al, 2021 [ 71 ]. For epitope prediction, an ABCpred Server was used, with a breakpoint of 0.8 and a window length of 12 to 16 residues [ 72 ].…”

Section: Methodsmentioning

confidence: 99%

Beyond Angiogenesis: The Multitasking Approach of the First PEGylated Vascular Endothelial Growth Factor (CdtVEGF) from Brazilian Rattlesnake Venom

Ferreira,

Oliveira,

Bordon

et al. 2023

Toxins

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A pioneering study regarding the isolation, biochemical evaluation, functional assays and first PEGylation report of a novel vascular endothelial growth factor from Crotalus durissus terrificus venom (CdtVEGF and PEG-CdtVEGF). CdtVEGF was isolated from crude venom using two different chromatographic steps, representing 2% of soluble venom proteins. Its primary sequence was determined using mass spectrometry analysis, and the molecule demonstrated no affinity to heparin. The Brazilian crotalid antivenom recognized CdtVEGF. Both native and PEGylated CdtVEGF were able to induce new vessel formation and migration, and to increase the metabolic activity of human umbilical endothelial vascular cells (HUVEC), resulting in better wound closure (~50% within 12 h) using the native form. CdtVEGF induced leukocyte recruitment to the peritoneal cavity in mice, with a predominance of neutrophil influx followed by lymphocytes, demonstrating the ability to activate the immune system. The molecule also induced a dose-dependent increase in vascular permeability, and PEG-CdtVEGF showed less in vivo inflammatory activity than CdtVEGF. By unraveling the intricate properties of minor components of snake venom like svVEGF, this study illuminates the indispensable significance of exploring these molecular tools to unveil physiological and pathological processes, elucidates the mechanisms of snakebite envenomings, and could possibly be used to design a therapeutic drug.

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“…One minor venom component, snake venom phosphodiesterase (svPDE), has been found to be ubiquitous in the venoms of most venomous species in Viperidae (~0.01 – 2.5%) (Damm, Hempel, & Sussmuth, 2021) and Elapidae (~0.4 – 1.1%) (Laustsen et al, 2015; C. H. Tan, Tan, Fung, & Tan, 2015). SvPDE is a soluble high-molecular-weight glycoprotein and is distinct from the intracellular phosphodiesterase (Al-Saleh & Khan, 2011; Mitra & Bhattacharyya, 2014; Oliveira et al, 2021; L. Peng et al, 2011; Santoro, Vaquero, Paes Leme, & Serrano, 2009; Trummal et al, 2014; Valerio, Corradini, Panunto, Mello, & Hyslop, 2002). Since extracellular ATP is involved in epithelial homeostasis (Mori et al, 2022) and also functions as a danger signal of damaged cells through the purinergic signaling pathway (Burnstock, 2016; Cintra-Francischinelli et al, 2010), svPDE, which enzymatically acts on the extracellular ATP, is expected to perturb the related physiological responses.…”

Section: Introductionmentioning

confidence: 99%

The evolution and structure of snake venom phosphodiesterase (svPDE) highlight its importance in venom actions

Pan

Lin

et al. 2022

Preprint

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For decades, studies of snake venoms focused on the venom-ome-specific toxins (VSTs). VSTs are dominant soluble proteins believed to contribute to the main venomous effects and emerged into gene clusters for fast adaptation and diversification of snake venoms. However, the conserved minor venom components, such as snake venom phosphodiesterase (svPDE), remain largely unexplored. Here, we focus on svPDE by genomic and transcriptomic analysis across snake clades and demonstrate that soluble svPDE is co-opted from the ancestral membrane-attached ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase 3) gene by replacing the original 5′ exon with the exon encoding a signal peptide. Notably, the exons, promoters and transcription/translation starts have been replaced multiple times during snake evolution, suggesting the evolutionary necessity of svPDE. The structural and biochemical analyses also show that svPDE shares the similar functions with ENPP family, suggesting its perturbation to the purinergic signaling and insulin transduction in venomous effects.

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Unraveling the structure and function of CdcPDE: A novel phosphodiesterase from Crotalus durissus collilineatus snake venom

Cited by 10 publications

References 84 publications

A Promising Biomolecule Able to Degrade Neutrophil Extracellular Traps: CdcPDE, a Rattlesnake Phosphodiesterase

A Promising Biomolecule Able to Degrade Neutrophil Extracellular Traps: CdcPDE, a Rattlesnake Phosphodiesterase

Beyond Angiogenesis: The Multitasking Approach of the First PEGylated Vascular Endothelial Growth Factor (CdtVEGF) from Brazilian Rattlesnake Venom

The evolution and structure of snake venom phosphodiesterase (svPDE) highlight its importance in venom actions

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