Characterization of thrombin inhibitory mechanism of rAaTI, a Kazal-type inhibitor from Aedes aegypti with anticoagulant activity

dc.contributor.authorWatanabe, Renata Midori Okuta [UNIFESP]
dc.contributor.authorTanaka-Azevedo, Anita M.
dc.contributor.authorAraujo, Mariana da Silva [UNIFESP]
dc.contributor.authorJuliano, Maria Aparecida [UNIFESP]
dc.contributor.authorTanaka, Aparecida Sadae [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionInst Butantan
dc.date.accessioned2016-01-24T14:06:12Z
dc.date.available2016-01-24T14:06:12Z
dc.date.issued2011-03-01
dc.description.abstractSaliva of blood-sucking arthropods contains a complex mixture of anti-haemostatic, anti-inflammatory and immune-modulator compounds. Among anti-haemostatic factors, there are anticoagulants, vasodilators and platelet aggregation inhibitors. Previous analyses of the sialotranscriptome of Aedes aegypti showed the potential presence of a Kazal-type serine protease inhibitor in the female salivary glands, carcass and also in the whole male, which inhibitor we named AaTI (A. aegypti thrombin inhibitor). Recently, we expressed and characterized rAaTI as a trypsin inhibitor, and its anticoagulant activity [1]. in this work we characterized the thrombin inhibition mechanism of rAaTI. Recombinant AaTI was able to prolong prothrombin time, activated partial thromboplastin time and thrombin time. in contrast, AaTI Delta (rAaTI truncated form) and C-terminal AaTI acidic tail prolong only thrombin time. in the competition assay, rAaTI, AaTI Delta or C-terminal AaTI acidic tail thrombin interactions seem to be affected by heparin but not by hirudin, suggesting that rAaTI binds to thrombin exosite 2. Finally, the thrombin inhibition assay of rAaTI showed an uncompetitive inhibition mechanism. in conclusion, rAaTI can probably inhibit thrombin by interacting with thrombin exosite 2, and the interaction is not mediated by the AaTI C-terminal region, since the truncated AaTI Delta form also prolongs thrombin time. (C) 2010 Elsevier Masson SAS. All rights reserved.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, Brazil
dc.description.affiliationInst Butantan, Lab Fisiopatol, BR-05503900 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIDFAPESP: 05/03514-9
dc.description.sponsorshipIDFAPESP: 07/56614-6
dc.description.sponsorshipIDCNPq: 470070/2004-8
dc.description.sponsorshipIDCNPq: 575829/2008-7
dc.format.extent618-623
dc.identifierhttp://dx.doi.org/10.1016/j.biochi.2010.12.006
dc.identifier.citationBiochimie. Paris: Elsevier France-editions Scientifiques Medicales Elsevier, v. 93, n. 3, p. 618-623, 2011.
dc.identifier.doi10.1016/j.biochi.2010.12.006
dc.identifier.fileWOS000288405600029.pdf
dc.identifier.issn0300-9084
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/33479
dc.identifier.wosWOS:000288405600029
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofBiochimie
dc.rightsAcesso aberto
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectAedes aegyptien
dc.subjectKazal-type inhibitoren
dc.subjectMidguten
dc.subjectSalivary glanden
dc.subjectThrombin inhibitoren
dc.titleCharacterization of thrombin inhibitory mechanism of rAaTI, a Kazal-type inhibitor from Aedes aegypti with anticoagulant activityen
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