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Biochemical, structural and functional evaluation of a phosphodiesterase from Crotalus durissus collilineatus venom

Grant number: 17/03580-9
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2018
Effective date (End): April 30, 2021
Field of knowledge:Health Sciences - Pharmacy - Toxicological Analysis
Principal researcher:Eliane Candiani Arantes Braga
Grantee:Isadora Sousa de Oliveira
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis, AP.TEM
Associated scholarship(s):18/21233-7 - Mass spectrometry analysis of a new phosphodiesterase from Crotalus durissus collilineatus venom, BE.EP.DR

Abstract

Snake venoms are represented by a wide range of components able to induce various pathological symptoms at envenoming victims, which is part of the neglected circumstances by WHO and is also a serious public health problem in Brazil. In the national territory, the genus Crotalus is represented by the snakes of species Crotalus durissus, scattered in several regions. Their venoms present a great complexity of protein components, being able to influence in the toxicity of the crotalic accident, hindering their treatment. In order to elucidate the toxicity mechanism of the various components is necessary the molecule isolation and its characterization. Thus, its action at envenoming becomes known, which facilitates the treatment of symptoms. Due to the complexity of C. d. collilineatus venom, many components have not yet been isolated, as phosphodiesterase (PDE). These enzymes are part of the nucleases, with DNAse and RNAse, and have a high molecular weight (90 ~160 kDa), and they can be found in monomeric or dimeric form. PDEs can be classified as 1 to 11 and they are responsible for breaking of phosphodiester bonds of nucleic acids, ATP, ADP, NAD, NGD, cAMP and cGMP, being able to interfere in physiological or pathological processes, which make them therapeutic targets of various diseases, besides acting as molecular tools. Their role in the snakebite envenoming is still not fully elucidated, but it is known that PDE is capable to leading to hypotension and locomotor depression of the prey and also capable of inhibiting platelet aggregation in vitro. Therefore, the aim of this study will perform the isolation of PDE from C. d. collilineatus venom, through the combination of liquid chromatography techniques, its identification by mass spectrometry techniques and amino-terminal sequencing, the determination of its molecular mass, build its three-dimensional model, evaluate its stability at different pH and temperature conditions, as well as to evaluate the phosphodiesterase activity on the bis(p-nitrophenyl)-phosphate substrate at different pH and temperature conditions and determine its kinetic parameters on the same substrate, evaluate the specificity of inhibition of the enzyme by 5 different inhibitors, verify that the antivenom produced in Brazil is able to recognize the PDE through indirect ELISA and perform platelet aggregation assay with this enzyme. In this way, the present study becomes relevant because will analyze a toxin that is important for the snakebite envenoming, but still little studied, increasing the knowledge about this enzymatic class. (AU)

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Scientific publications (11)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PARENTE, JULIANA MONTENEGRO; MELLO, MARCELA MARIA BLASCKE DE; SILVA, PEDRO HENRIQUE LEITE DA; OMOTO, ANA CAROLINA MIEKO; PERNOMIAN, LAENA; OLIVEIRA, ISADORA SOUSA DE; MAHMUD, ZABED; FAZAN, JR., RUBENS; ARANTES, ELIANE CANDIANI; SCHULZ, RICHARD; CASTRO, MICHELE MAZZARON DE. MMP inhibition attenuates hypertensive eccentric cardiac hypertrophy and dysfunction by preserving troponin I and dystrophin. Biochemical Pharmacology, v. 193, NOV 2021. Web of Science Citations: 0.
FERREIRA, ISABELA GOBBO; PUCCA, MANUELA BERTO; DE OLIVEIRA, ISADORA SOUSA; CERNI, FELIPE AUGUSTO; JACOB, BEATRIZ DE CASSIA DA SILVA; ARANTES, ELIANE CANDIANI. Snake venom vascular endothelial growth factors (svVEGFs): Unravelling their molecular structure, functions, and research potential. CYTOKINE & GROWTH FACTOR REVIEWS, v. 60, p. 133-143, AUG 2021. Web of Science Citations: 0.
PUCCA, MANUELA B.; BERNARDE, PAULO SERGIO; ROCHA, ANDERSON MACIEL; VIANA, PATRIK F.; FARIAS, RAIMUNDO ERASMO SOUZA; CERNI, FELIPE A.; OLIVEIRA, ISADORA S.; FERREIRA, ISABELA G.; SANDRI, ELISEU A.; SACHETT, JACQUELINE; WEN, FAN HUI; SAMPAIO, VANDERSON; LAUSTSEN, ANDREAS H.; SARTIM, MARCO A.; MONTEIRO, WUELTON M. rotalus Durissus Ruruima: Current Knowledge on Natural History, Medical Importance, and Clinical Toxinolog. FRONTIERS IN IMMUNOLOGY, v. 12, JUN 8 2021. Web of Science Citations: 0.
DE OLIVEIRA, ISADORA SOUSA; PUCCA, MANUELA BERTO; WIEZEL, GISELE ADRIANO; CARDOSO, IARA AIME; FIGUEIREDO BORDON, KARLA DE CASTRO; SARTIM, MARCO AURELIO; KALOGEROPOULOS, KONSTANTINOS; AHMADI, SHIRIN; BAIWIR, DOMINIQUE; NONATO, MARIA CRISTINA; SAMPAIO, SUELY VILELA; LAUSTSEN, ANDREAS HOUGAARD; DEM KELLER, ULRICH AUF; QUINTON, LOIC; ARANTES, ELIANE CANDIANI. Unraveling the structure and function of CdcPDE: A novel phosphodiesterase from Crotalus durissus collilineatus snake venom. International Journal of Biological Macromolecules, v. 178, p. 180-192, MAY 1 2021. Web of Science Citations: 0.
PUCCA, MANUELA B.; KNUDSEN, CECILIE; S. OLIVEIRA, ISADORA; RIMBAULT, CHARLOTTE; A. CERNI, FELIPE; WEN, FAN HUI; SACHETT, JACQUELINE; SARTIM, MARCO A.; LAUSTSEN, ANDREAS H.; MONTEIRO, WUELTON M. Current Knowledge on Snake Dry Bites. TOXINS, v. 12, n. 11 NOV 2020. Web of Science Citations: 1.
CAMPOS, LUCAS B.; PUCCA, MANUELA B.; SILVA, LUCIANO C.; PESSENDA, GABRIELA; FILARDI, BRUNO A.; CERNI, FELIPE A.; OLIVEIRA, ISADORA S.; LAUSTSEN, ANDREAS H.; ARANTES, ELIANE C.; BARBOSA, JOSE E. Identification of cross-reactive human single-chain variable fragments against phospholipases A(2) from Lachesis muta and Bothrops spp venoms. Toxicon, v. 184, p. 116-121, SEP 2020. Web of Science Citations: 0.
ABREU, CAIO B.; BORDON, KARLA C. F.; CERNI, FELIPE A.; OLIVEIRA, ISADORA S.; BALENZUELA, CARLA; ALEXANDRE-SILVA, GABRIEL M.; ZOCCAL, KARINA F.; REIS, MOUZARLLEM B.; WIEZEL, GISELE A.; PEIGNEUR, STEVE; PINHEIRO-JUNIOR, ERNESTO L.; TYTGAT, JAN; CUNHA, TIAGO M.; QUINTON, LOIC; FACCIOLI, LUCIA H.; ARANTES, ELIANE C.; ZOTTICH, UMBERTO; PUCCA, MANUELA B. Pioneering Study onRhopalurus crassicaudaScorpion Venom: Isolation and Characterization of the Major Toxin and Hyaluronidase. FRONTIERS IN IMMUNOLOGY, v. 11, AUG 20 2020. Web of Science Citations: 0.
FIGUEIREDO BORDON, KARLA DE CASTRO; COLOGNA, CAMILA TAKENO; FORNARI-BALDO, ELISA CORREA; PINHEIRO-JUNIOR, ERNESTO LOPES; CERNI, FELIPE AUGUSTO; AMORIM, FERNANDA GOBBI; PINO ANJOLETTE, FERNANDO ANTONIO; CORDEIRO, FRANCIELLE ALMEIDA; WIEZEL, GISELE ADRIANO; CARDOSO, IARA AIME; FERREIRA, ISABELA GOBBO; DE OLIVEIRA, ISADORA SOUSA; BOLDRINI-FRANCA, JOHARA; PUCCA, MANUELA BERTO; BALDO, MATEUS AMARAL; ARANTES, ELIANE CANDIANI. From Animal Poisons and Venoms to Medicines: Achievements, Challenges and Perspectives in Drug Discovery. FRONTIERS IN PHARMACOLOGY, v. 11, JUL 24 2020. Web of Science Citations: 14.
MANUELA B. PUCCA; MICHELLE V. S. FRANCO; JILVANDO M. MEDEIROS; ISADORA S. OLIVEIRA; SHIRIN AHMADI; FELIPE A. CERNI; UMBERTO ZOTTICH; BRUNA K. BASSOLI; WUELTON M. MONTEIRO; ANDREAS H. LAUSTSEN. Chronic kidney failure following lancehead bite envenoming: a clinical report from the Amazon region. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 26, p. -, 2020. Web of Science Citations: 1.
PUCCA, MANUELA B.; CERNI, FELIPE A.; OLIVEIRA, ISADORA S.; JENKINS, TIMOTHY P.; ARGEMI, LIDIA; SORENSEN, CHRISTOFFER V.; AHMADI, SHIRIN; BARBOSA, JOSE E.; LAUSTSEN, ANDREAS H. Bee Updated: Current Knowledge on Bee Venom and Bee Envenoming Therapy. FRONTIERS IN IMMUNOLOGY, v. 10, SEP 6 2019. Web of Science Citations: 3.
OLIVEIRA, ISADORA S.; FERREIRA, ISABELA G.; ALEXANDRE-SILVA, GABRIEL M.; CERNI, FELIPE A.; CREMONEZ, CAROLINE M.; ARANTES, ELIANE C.; ZOTTICH, UMBERTO; PUCCA, MANUELA B. Scorpion toxins targeting Kv1.3 channels: insights into immunosuppression. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 25, APR 15 2019. Web of Science Citations: 1.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
OLIVEIRA, Isadora Sousa de. Biochemical, structural and functional evaluation of a phosphodiesterase from Crotalus durissus collilineatus venom. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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