Molecular dynamics and circular dichroism studies of human and rat C-peptides

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dc.contributor.authorMares-Guia, Thiago Renno
dc.contributor.authorMaigret, Bernard
dc.contributor.authorMartins, Natalia Florencio
dc.contributor.authorTurchetti Maia, Ana Luiza
dc.contributor.authorVilela, Luciano
dc.contributor.authorInacio Ramos, Carlos Henrique
dc.contributor.authorNeto, Luiz Juliano
dc.contributor.authorJuliano, Maria Aparecida
dc.contributor.authorMares-Guia, Marcos Luiz dos
dc.contributor.authorSantoro, Marcelo Matos
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.contributor.institutionHenri Poincare Univ
dc.contributor.institutionUniversidade de Brasília (UnB)
dc.contributor.institutionEmpresa Brasileira de Pesquisa Agropecuária (EMBRAPA)
dc.contributor.institutionBiomm SA
dc.contributor.institutionLab Nacl Luz Sincrotron
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T12:41:38Z
dc.date.available2016-01-24T12:41:38Z
dc.date.issued2006-12-01
dc.description.abstractProinsulin C-peptide has been recently described as an endogenous peptide hormone, responsible for important physiological functions others than its role in proinsulin processing. Accumulating evidences that C-peptide exerts beneficial effects in the treatment of long term complications of patients with type I diabetes mellitus indicate that this molecule may be administered together with insulin in future therapies. Despite its clear pharmacological interest, the secondary and three-dimensional (3D) structures of human C-peptide are still points of controversy. in the present work we report molecular dynamics (MD) simulations of human, rat I and rat II C-peptides. A common experimental strategy applied to all peptides consisted of homology building followed by multinanosecond MD simulations in vacuum and water. Circular dichroism (CD) experiments of each peptide in the absence and presence of 2,2,2-trifluoroethanol (TFE) were performed to support validation of the theoretical models. A multiple sequence alignment of 23 known mammalian C-peptides was constructed to identify significant conserved sites that would be important for the maintenance of secondary and tertiary structures. the analysis of the molecular dynamics trajectories for the human, rat I and rat II molecules have shown quite different general behavior, being the human C-peptide more flexible than the two others. Human and rat C-peptides exhibit very stable turn-like structures at the middle and C-terminal regions, which have been described as potential active sites of C-peptides. Human C-peptide also presented a short alpha-helix throughout the MD, which was not found in the rat molecules. CD data is in very good agreement with the MD results and both methods were able to identify a greater structural stability and potential in rat C-peptides when compared to the human C-peptide. the simulation results are discussed and validated in the light of multiple sequence alignment, recent experimental data from the literature and our own CD experiments. (c) 2006 Published by Elsevier Inc.en
dc.description.affiliationUniv Fed Minas Gerais, Dept Bioquim & Imunol, BR-31270901 Belo Horizonte, MG, Brazil
dc.description.affiliationHenri Poincare Univ, CNRS, UHP, UMR 7565,eDAM Grp, Vandoeuvre Les Nancy, France
dc.description.affiliationUniv Brasilia, BR-70910900 Brasilia, DF, Brazil
dc.description.affiliationEMBRAPA, Recursos Genet & Biotecnol, Lab Bioinformat, BR-70770900 Brasilia, DF, Brazil
dc.description.affiliationBiomm SA, Praca Carlos Chagas, BR-30170020 Belo Horizonte, MG, Brazil
dc.description.affiliationLab Nacl Luz Sincrotron, Ctr Biol Mol Estrutural, BR-13084971 Campinas, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, BR-04044020 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent532-542
dc.identifierhttp://dx.doi.org/10.1016/j.jmgm.2006.03.002
dc.identifier.citationJournal of Molecular Graphics & Modelling. New York: Elsevier B.V., v. 25, n. 4, p. 532-542, 2006.
dc.identifier.doi10.1016/j.jmgm.2006.03.002
dc.identifier.issn1093-3263
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/29290
dc.identifier.wosWOS:000242797400015
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofJournal of Molecular Graphics & Modelling
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectC-peptideen
dc.subjecthomology buildingen
dc.subjectmolecular dynamicsen
dc.subjectcircular dichroismen
dc.subjectdiabetes mellitusen
dc.titleMolecular dynamics and circular dichroism studies of human and rat C-peptidesen
dc.typeinfo:eu-repo/semantics/article
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