A structure-based proposal for a comprehensive myotoxic mechanism of phospholipase A(2)-like proteins from viperid snake venoms

dc.contributorUniversidade Estadual Paulista (Unesp)
dc.contributorUniv Costa Rica
dc.creatorFernandes, Carlos A. H. [UNESP]
dc.creatorBorges, Rafael J. [UNESP]
dc.creatorLomonte, Bruno
dc.creatorFontes, Marcos R. M. [UNESP]
dc.date2015-03-18T15:53:19Z
dc.date2015-03-18T15:53:19Z
dc.date2014-12-01
dc.date.accessioned2023-09-09T11:04:53Z
dc.date.available2023-09-09T11:04:53Z
dc.identifierhttp://dx.doi.org/10.1016/j.bbapap.2014.09.015
dc.identifierBiochimica Et Biophysica Acta-proteins And Proteomics. Amsterdam: Elsevier Science Bv, v. 1844, n. 12, p. 2265-2276, 2014.
dc.identifier1570-9639
dc.identifierhttp://hdl.handle.net/11449/116448
dc.identifier10.1016/j.bbapap.2014.09.015
dc.identifierWOS:000345182800023
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8765933
dc.descriptionEnvenomation via snakebites is an important public health problem in many tropical and subtropical countries that, in addition to mortality, can result in permanent sequelae as a consequence of local tissue damage, which represents a major challenge to antivenom therapy. Venom phospholipases A(2) (PLA(2)s) and PLA(2)-like proteins play a leading role in the complex pathogenesis of skeletal muscle necrosis, nevertheless their precise mechanism of action is only partially understood. Recently, detailed structural information has been obtained for more than twenty different members of the PLA(2)-like myotoxin subfamily. In this review, we integrate the available structural, biochemical and functional data on these toxins and present a comprehensive hypothesis for their myotoxic mechanism. This process involves an allosteric transition and the participation of two independent interaction sites for docking and disruption of the target membrane, respectively, leading to a five-step mechanism of action. Furthermore, recent functional and structural studies of these toxins complexed with ligands reveal diverse neutralization mechanisms that can be classified into at least three different groups. Therefore, the data summarized here for the PLA(2)-like myotoxins could provide a useful molecular basis for the search for novel neutralizing strategies to improve the treatment of envenomation by viperid snakes. (C) 2014 Elsevier B.V. All rights reserved.
dc.descriptionUNESP, Inst Biociencias, Dept Fis & Biofis, BR-18618970 Botucatu, SP, Brazil
dc.descriptionUniv Costa Rica, Fac Microbiol, Inst Clodomiro Picado, San Jose 11501, Costa Rica
dc.descriptionUNESP, Inst Biociencias, Dept Fis & Biofis, BR-18618970 Botucatu, SP, Brazil
dc.format2265-2276
dc.languageeng
dc.publisherElsevier B.V.
dc.relationBiochimica Et Biophysica Acta-proteins And Proteomics
dc.relation2.609
dc.relation1,170
dc.rightsAcesso restrito
dc.sourceWeb of Science
dc.subjectSnake venom
dc.subjectMyotoxin
dc.subjectPhospholipase A(2)
dc.subjectLys49
dc.subjectInhibitor
dc.subjectMyonecrosis
dc.titleA structure-based proposal for a comprehensive myotoxic mechanism of phospholipase A(2)-like proteins from viperid snake venoms
dc.typeArtigo


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