Crystallographic portrayal of different conformational states of a Lys49 phospholipase A2 homologue: Insights into structural determinants for myotoxicity and dimeric configuration

Página do item simplificado
dc.contributor.authorUllah, A. [UNESP]
dc.contributor.authorSouza, T. A C B
dc.contributor.authorBetzel, C.
dc.contributor.authorMurakami, M. T.
dc.contributor.authorArni, R. K. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionCentro Nacional de Pesquisa em Energia e Materiais
dc.contributor.institutionLaboratory of Structural Biology of Infection and Inflammation, C/o DESY
dc.date.accessioned2014-05-27T11:27:03Z
dc.date.available2014-05-27T11:27:03Z
dc.date.issued2012-10-01
dc.description.abstractCatalytically inactive phospholipase A2 (PLA2) homologues play key roles in the pathogenesis induced by snake envenomation, causing extensive tissue damage via a mechanism still unknown. Although, the amino acid residues directly involved in catalysis are conserved, the substitution of Asp49 by Arg/Lys/Gln or Ser prevents the binding of the essential calcium ion and hence these proteins are incapable of hydrolyzing phospholipids. In this work, the crystal structure of a Lys49-PLA2 homologue from Bothrops brazili (MTX-II) was solved in two conformational states: (a) native, with Lys49 singly coordinated by the backbone oxygen atom of Val31 and (b) complexed with tetraethylene glycol (TTEG). Interestingly, the TTEG molecule was observed in two different coordination cages depending on the orientation of the nominal calcium-binding loop and of the residue Lys49. These structural observations indicate a direct role for the residue Lys49 in the functioning of a catalytically inactive PLA2 homologue suggesting a contribution of the active site-like region in the expression of pharmacological effects such as myotoxicity and edema formation. Despite the several crystal structures of Lys49-PLA2 homologues already determined, their biological assembly remains controversial with two possible conformations. The extended dimer with the hydrophobic channel exposed to the solvent and the compact dimer in which the active site-like region is occluded by the dimeric interface. In the MTX-II crystal packing analysis was found only the extended dimer as a possible stable quaternary arrangement. © 2012 Elsevier B.V.en
dc.description.affiliationCentro Multiusuário de Inovação Biomolecular Departamento de Física Universidade Estadual Paulista (UNESP), São José do Rio Preto-SP 15054-000 SP
dc.description.affiliationLaboratório Nacional de Biociências Centro Nacional de Pesquisa em Energia e Materiais, Campinas, 13083-970 SP
dc.description.affiliationInstitute of Biochemistry and Molecular Biology University of Hamburg Laboratory of Structural Biology of Infection and Inflammation, C/o DESY, Notkestrasse 85, Build. 22a, D-22603 Hamburg
dc.description.affiliationUnespCentro Multiusuário de Inovação Biomolecular Departamento de Física Universidade Estadual Paulista (UNESP), São José do Rio Preto-SP 15054-000 SP
dc.format.extent209-214
dc.identifierhttp://dx.doi.org/10.1016/j.ijbiomac.2012.05.006
dc.identifier.citationInternational Journal of Biological Macromolecules, v. 51, n. 3, p. 209-214, 2012.
dc.identifier.doi10.1016/j.ijbiomac.2012.05.006
dc.identifier.file2-s2.0-84863619113.pdf
dc.identifier.issn0141-8130
dc.identifier.issn1879-0003
dc.identifier.lattes9162508978945887
dc.identifier.orcid0000-0003-2460-1145
dc.identifier.scopus2-s2.0-84863619113
dc.identifier.urihttp://hdl.handle.net/11449/73606
dc.language.isoeng
dc.relation.ispartofInternational Journal of Biological Macromolecules
dc.relation.ispartofjcr3.909
dc.relation.ispartofsjr0,917
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectBothrops brazili
dc.subjectConformational states
dc.subjectLys49 phospholipase A2 homologue
dc.subjectOligomerization
dc.subjectTetraethylene glycol
dc.subjectdimer
dc.subjectglycol
dc.subjectlysine
dc.subjectmyotoxin ii
dc.subjectphospholipase A2
dc.subjectsnake venom
dc.subjecttetraethylene glycol
dc.subjectunclassified drug
dc.subjectBothrops
dc.subjectcalcium binding
dc.subjectcatalysis
dc.subjectcomplex formation
dc.subjectcrystal structure
dc.subjectcrystallography
dc.subjectenzyme conformation
dc.subjectmyotoxicity
dc.subjectoligomerization
dc.subjectprotein assembly
dc.subjectprotein expression
dc.subjectsolvent effect
dc.subjectstructure analysis
dc.subjecttoxicity
dc.subjectAnimals
dc.subjectCatalytic Domain
dc.subjectEthylene Glycols
dc.subjectLigands
dc.subjectModels, Molecular
dc.subjectMutant Proteins
dc.subjectPhospholipases A2
dc.subjectProtein Conformation
dc.subjectProtein Multimerization
dc.subjectProtein Structure, Secondary
dc.titleCrystallographic portrayal of different conformational states of a Lys49 phospholipase A2 homologue: Insights into structural determinants for myotoxicity and dimeric configurationen
dc.typeArtigo
dcterms.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
unesp.author.lattes9162508978945887[5]
unesp.author.orcid0000-0003-2460-1145[5]
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências Letras e Ciências Exatas, São José do Rio Pretopt

Arquivos

Pacote Original
Agora exibindo 1 - 1 de 1
Imagem de Miniatura
Nome:
2-s2.0-84863619113.pdf
Tamanho:
768.47 KB
Formato:
Adobe Portable Document Format
Baixar

Coleções

Artigos - Física - IBILCE