Inhibition of myotoxic activity of Bothrops asper myotoxin II by the anti-trypanosomal drug surarnin

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorMurakami, M. T.
dc.creatorArruda, E. Z.
dc.creatorMelo, P. A.
dc.creatorMartinez, A. B.
dc.creatorCalil-Elias, S.
dc.creatorTomaz, M. A.
dc.creatorLomonte, B.
dc.creatorGutierrez, J. M.
dc.creatorArni, R. K.
dc.date2014-05-20T14:02:25Z
dc.date2016-10-25T17:09:06Z
dc.date2014-05-20T14:02:25Z
dc.date2016-10-25T17:09:06Z
dc.date2005-07-15
dc.date.accessioned2017-04-05T21:27:32Z
dc.date.available2017-04-05T21:27:32Z
dc.identifierJournal of Molecular Biology. London: Academic Press Ltd Elsevier B.V. Ltd, v. 350, n. 3, p. 416-426, 2005.
dc.identifier0022-2836
dc.identifierhttp://hdl.handle.net/11449/22007
dc.identifierhttp://acervodigital.unesp.br/handle/11449/22007
dc.identifier10.1016/j.jmb.2005.04.072
dc.identifierWOS:000230296700003
dc.identifierhttp://dx.doi.org/10.1016/j.jmb.2005.04.072
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/867480
dc.descriptionSuramin, a synthetic polysulfonated compound, developed initially for the treatment of African trypanosomiasis and onchocerciasis, is currently used for the treatment of several medically relevant disorders. Suramin, heparin, and other polyanions inhibit the myotoxic activity of Lys49 phospholipase A(2) analogues both in vitro and in vivo, and are thus of potential importance as therapeutic agents in the treatment of viperid snake bites. Due to its conformational flexibility around the single bonds that link the central phenyl rings to the secondary amide backbone, the symmetrical suramin molecule binds by an induced-fit mechanism complementing the hydrophobic surfaces of the dimer and adopts a novel conformation that lacks C2 symmetry in the dimeric crystal structure of the suramin-Bothrops asper myotoxin II complex. The simultaneous binding of suramin at the surfaces of the two monomers partially restricts access to the nominal active sites and significantly changes the overall charge of the interfacial recognition face of the protein, resulting in the inhibition of myotoxicity. (c) 2005 Elsevier Ltd. All rights reserved.
dc.languageeng
dc.publisherElsevier B.V.
dc.relationJournal of Molecular Biology
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectsuramin
dc.subjectheparin
dc.subjectmyotoxicity
dc.subjectinhibition
dc.subjectCrystal structure
dc.titleInhibition of myotoxic activity of Bothrops asper myotoxin II by the anti-trypanosomal drug surarnin
dc.typeOtro


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