Insularinase A, a prothrombin activator from Bothrops insularis venom, is a metalloprotease derived from a gene encoding protease and disintegrin domains

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dc.contributor.authorModesto, JCD
dc.contributor.authorJunqueira-de-Azevedo, ILM
dc.contributor.authorNeves-Ferreira, AGC
dc.contributor.authorFritzen, M.
dc.contributor.authorOliva, MLV
dc.contributor.authorHo, P. L.
dc.contributor.authorPerales, J.
dc.contributor.authorChudzinski-Tavassi, A. M.
dc.contributor.institutionInst Butantan
dc.contributor.institutionInst Burantan
dc.contributor.institutionFiocruz MS
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2016-01-24T12:37:54Z
dc.date.available2016-01-24T12:37:54Z
dc.date.issued2005-06-01
dc.description.abstractThe first low-molecular-mass metalloprotease presenting prothrombin activating activity was purified from Bothrops insularis venom and named insularinase A. It is a single-chain protease with a molecular mass of 22 639 Da. cDNA sequence analysis revealed that the disintegrin domain of the precursor protein is post-translationally processed, producing the mature insularinase A. Analysis of its deduced amino acid sequence showed a high similarity with several fibrin(ogen)olytic metalloproteases and only a moderate similarity with prothrombin activators. However, SIDS-PAGE of prothrombin after activation by insularinase A showed fragment patterns similar to those generated by group A prothrombin activators, which convert prothrombin into meizothrombin independently of the prothrombinase complex. in addition, insularinase A activates factor X and hydrolyses fibrinogen and fibrin. Chelating agents fully inhibit all insularinase A activities. Insularinase A induced neither detachment nor apoptosis of human endothelial cells and was also not able to trigger an endothelial proinflammatory cell response. Nitric oxide and prostacyclin levels released by endothelial cells were significantly increased after treatment with insularinase A. Our results show that, although its primary structure is related to class P-I fibrin(ogen)olytic metalloproteases, insularinase A is functionally similar to group A prothrombin activators.en
dc.description.affiliationInst Butantan, Lab Bioquim & Biofis, BR-05503900 São Paulo, Brazil
dc.description.affiliationInst Burantan, Ctr Biotecnol, BR-05503900 São Paulo, Brazil
dc.description.affiliationFiocruz MS, Inst Osvaldo, Dept Fisiol & Farmacodinamica, BR-21045900 Rio de Janeiro, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Bioquim, BR-0550801 São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Inst Biociencias, BR-0550801 São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Inst Quim, BR-0550801 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Bioquim, BR-0550801 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent589-600
dc.identifierhttp://dx.doi.org/10.1515/BC.2005.069
dc.identifier.citationBiological Chemistry. Berlin: Walter de Gruyter Gmbh, v. 386, n. 6, p. 589-600, 2005.
dc.identifier.doi10.1515/BC.2005.069
dc.identifier.issn1431-6730
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/28341
dc.identifier.wosWOS:000230256800010
dc.language.isoeng
dc.publisherWalter de Gruyter Gmbh
dc.relation.ispartofBiological Chemistry
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectBothrops insularisen
dc.subjectcoagulationen
dc.subjectendothelial cellen
dc.subjectmetalloproteaseen
dc.subjectprothrombin activatoren
dc.subjectsnake venomen
dc.titleInsularinase A, a prothrombin activator from Bothrops insularis venom, is a metalloprotease derived from a gene encoding protease and disintegrin domainsen
dc.typeinfo:eu-repo/semantics/article
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