Dissociation of enzymatic and pharmacological properties of piratoxins-I and -III, two myotoxic phospholipases A2 from Bothrops pirajai snake venom
| Autor: | Andreimar M. Soares, Richard J. Ward, R.K. Bortoleto, S. H. Andrião-Escarso, José María Gutiérrez, Léa Rodrigues-Simioni, Raghuvir K. Arni, José Roberto Giglio |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Male
Pharmacological Activities Snake venom Myotoxin Diaphragm Biophysics Neuromuscular transmission Chemical Modifications Microbial Sensitivity Tests Reptilian Proteins In Vitro Techniques Crystallography X-Ray Group II Phospholipases A2 Biochemistry Phospholipases A Protein Structure Secondary Mice Structure-Activity Relationship Crotalid Venoms Animals Edema Structure–activity relationship Bothrops Cyanogen Bromide Enzyme Inhibitors Molecular Biology Bothrops pirajai Nitrobenzenes Peroxidase chemistry.chemical_classification Sequence Homology Amino Acid biology Muscles Circular Dichroism Acetophenones biology.organism_classification Phospholipases A2 Enzyme chemistry Liposomes Crystal Structure Bothrops Pirajai Biological Assay Myotoxins |
| Zdroj: | Archives of Biochemistry and Biophysics; Volumen 387, Número 2. 2001 Kérwá Universidad de Costa Rica instacron:UCR |
| Popis: | Piratoxins (PrTX) I and III are phospholipases A2 (PLA2s) or PLA2 homologue myotoxins isolated from Bothrops pirajai snake venom, which also induce myonecrosis, bactericidal activity against Escherichia coli, disruption of artificial membranes, and edema. PrTX-III is a catalytically active hemolytic and anticoagulant Asp49 PLA2, while PrTX-I is a Lys49 PLA2 homologue, which is catalytically inactive on artificial substrates, but promotes blockade of neuromuscular transmission. Chemical modifications of His, Lys, Tyr, and Trp residues of PrTX-I and PrTX-III were performed, together with cleavage of the N-terminal octapeptide by CNBr and inhibition by heparin and EDTA. The lethality, bactericidal activity, myotoxicity, neuromuscular effect, edema inducing effect, catalytic and anticoagulant activities, and the liposome-disruptive activity of the modified toxins were evaluated. A complex pattern of functional differences between the modified and native toxins was observed. However, in general, chemical modifications that significantly affected the diverse pharmacological effects of the toxins did not influence catalytic or membrane disrupting activities. Analysis of structural changes by circular dichroism spectroscopy demonstrated significant changes in the secondary structure only in the case of N-terminal octapeptide cleavage. These data indicate that PrTX-I and PrTX-III possess regions other than the catalytic site, which determine their toxic and pharmacological activities. Fundação de Amparo à Pesquisa do Estado de São Paulo//FAPESP/Brasil Conselho Nacional de Desenvolvimento Científico e Tecnológico//CNPq/Brasil Universidad de Costa Rica//UCR/Costa Rica UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|