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Structural Basis for the Inhibition of a Phospholipase A2-Like Toxin by Caffeic and Aristolochic Acids

Fernandes, Carlos A H ; Cardoso, Fábio Florença ; Cavalcante, Walter G L ; Soares, Andreimar M ; Dal-Pai, Maeli ; Gallacci, Marcia ; Fontes, Marcos R M Silman, Israel

PloS one, 2015-07, Vol.10 (7), p.e0133370 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Structural Basis for the Inhibition of a Phospholipase A2-Like Toxin by Caffeic and Aristolochic Acids
Autor: Fernandes, Carlos A H ; Cardoso, Fábio Florença ; Cavalcante, Walter G L ; Soares, Andreimar M ; Dal-Pai, Maeli ; Gallacci, Marcia ; Fontes, Marcos R M
Silman, Israel
Assuntos: Acids ; Animals ; Antidotes - chemistry ; Antidotes - pharmacology ; Aristolochic Acids - chemistry ; Aristolochic Acids - pharmacology ; Bothrops - metabolism ; Caffeic Acids - chemistry ; Caffeic Acids - pharmacology ; Complications ; Crotalid Venoms - antagonists & inhibitors ; Crotalid Venoms - chemistry ; Crotalid Venoms - metabolism ; Crystallography, X-Ray ; Developing countries ; Drug Discovery ; Folk medicine ; Group II Phospholipases A2 - antagonists & inhibitors ; Group II Phospholipases A2 - chemistry ; Group II Phospholipases A2 - metabolism ; Injuries ; Injury prevention ; LDCs ; Ligands ; Medicinal plants ; Mice ; Models, Molecular ; Muscles ; Muscles - drug effects ; Muscles - pathology ; Muscles - physiopathology ; Musculoskeletal system ; Phospholipase ; Phospholipase A2 ; Protein Conformation ; Proteins ; Reptilian Proteins - antagonists & inhibitors ; Reptilian Proteins - chemistry ; Reptilian Proteins - metabolism ; Skeletal muscle ; Snake bites ; Snakes ; Social conditions ; Social problems ; Structure-function relationships ; Studies ; Toxicology ; Tropical diseases ; Venom
É parte de: PloS one, 2015-07, Vol.10 (7), p.e0133370
Notas: Conceived and designed the experiments: CAHF WGLC AMS MG MRMF. Performed the experiments: CAHF FFC WGLC AMS. Analyzed the data: CAHF FFC WGLC AMS MDP MG MRMF. Contributed reagents/materials/analysis tools: AMS MDP MG MRMF. Wrote the paper: CAHF FFC WGLC MG MRMF.
Competing Interests: The authors have declared that no competing interests exist.
Descrição: One of the main challenges in toxicology today is to develop therapeutic alternatives for the treatment of snake venom injuries that are not efficiently neutralized by conventional serum therapy. Venom phospholipases A2 (PLA2s) and PLA2-like proteins play a fundamental role in skeletal muscle necrosis, which can result in permanent sequelae and disability. This leads to economic and social problems, especially in developing countries. In this work, we performed structural and functional studies with Piratoxin-I, a Lys49-PLA2 from Bothropspirajai venom, complexed with two compounds present in several plants used in folk medicine against snakebites. These ligands partially neutralized the myotoxic activity of PrTX-I towards binding on the two independent sites of interaction between Lys49-PLA2 and muscle membrane. Our results corroborate the previously proposed mechanism of action of PLA2s-like and provide insights for the design of structure-based inhibitors that could prevent the permanent injuries caused by these proteins in snakebite victims.
Editor: United States: Public Library of Science
Idioma: Inglês

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Structural Basis for the Inhibition of a Phospholipase A2-Like Toxin by Caffeic and Aristolochic Acids

Fernandes, Carlos A H ; Cardoso, Fábio Florença ; Cavalcante, Walter G L ; Soares, Andreimar M ; Dal-Pai, Maeli ; Gallacci, Marcia ; Fontes, Marcos R M Silman, Israel

United States: Public Library of Science

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