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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Paulistine-The Functional Duality of a Wasp Venom Peptide Toxin

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Arcuri, Helen Andrade [1, 2] ; Gomes, Paulo Cesar [1, 3] ; de Souza, Bibiana Monson [1] ; Dias, Nathalia Baptista [1] ; Brigatte, Patricia [2] ; Stabeli, Rodrigo Guerino [2] ; Palma, Mario Sergio [1]
Total Authors: 7
[1] Sao Paulo State Univ UNESP, Inst Biosci, Ctr Study Social Insects, Dept Biol, BR-13506900 Rio Claro, SP - Brazil
[2] Fundacao Oswaldo Cruz, Hlth Minist Fiocruz Rondonia, BR-21040900 Porto Velho, RO - Brazil
[3] Sao Paulo State Univ UNESP, Dept Clin Anal, Prote Ctr, Fac Pharmaceut, Sci, BR-14801902 Araraquara, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: TOXINS; v. 8, n. 3 MAR 2016.
Web of Science Citations: 3

It has been reported that Paulistine in the venom of the wasp Polybia paulista co-exists as two different forms: an oxidized form presenting a compact structure due to the presence of a disulfide bridge, which causes inflammation through an apparent interaction with receptors in the 5-lipoxygenase pathway, and a naturally reduced form (without the disulfide bridge) that exists in a linear conformation and which also causes hyperalgesia and acts in the cyclooxygenase type II pathway. The reduced peptide was acetamidomethylated (Acm-Paulistine) to stabilize this form, and it still maintained its typical inflammatory activity. Oxidized Paulistine docks onto PGHS2 (COX-2) molecules, blocking the access of oxygen to the heme group and inhibiting the inflammatory activity of Acm-Paulistine in the cyclooxygenase type II pathway. Docking simulations revealed that the site of the docking of Paulistine within the PGHS2 molecule is unusual among commercial inhibitors of the enzyme, with an affinity potentially much higher than those observed for traditional anti-inflammatory drugs. Therefore, Paulistine causes inflammatory activity at the level of the 5-lipooxygenase pathway and, in parallel, it competes with its reduced form in relation to the activation of the cyclooxygenase pathway. Thus, while the reduced Paulistine causes inflammation, its oxidized form is a potent inhibitor of this activity. (AU)

FAPESP's process: 11/51684-1 - System biology as experimental strategy for discovery of novel natural products in the fauna of venomous arthropods from São Paulo State
Grantee:Mario Sergio Palma
Support type: BIOTA-FAPESP Program - Thematic Grants