Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Structural Findings and Molecular Modeling Approach of a TFPI-Like Inhibitor

Texto completo
Autor(es):
Mesquita Pasqualoto, Kerly Fernanda [1] ; Balan, Andrea [2] ; Barreto, Sandra Alves [1] ; Simons, Simone Michaela [1] ; Chudzinski-Tavassi, Ana Marisa [1]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Inst Butantan, Lab Bioquim & Biofis, BR-05503900 Sao Paulo - Brazil
[2] Brazilian Natl Lab Biosci, Ctr Struct & Mol Biol, BR-13084971 Campinas, SP - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: PROTEIN AND PEPTIDE LETTERS; v. 21, n. 5, p. 452-457, MAY 2014.
Citações Web of Science: 6
Resumo

Specific blood coagulation inhibitors from hematophagous organisms, with different structures and novel mechanism of action, have been described and they represent promising agents for the treatment of a variety of human diseases related to coagulation and cancer. In our lab, the salivary glands transcriptome of the adult Amblyomma cajennense tick was previously characterized by expressed sequence tags (EST). A transcript that codes for a tissue factor pathway inhibitor (TFPI)-like protein with unique structure was found, and the recombinant form of this protein was named Amblyomin-X. This protein was able to inhibit the factor Xa amidolytic activity and the activation of factor X by the extrinsic tenase complex (FVIIa/TF). Herein, it was performed functional and structural evaluation of Amblyomin-X. The CD assay and molecular dynamics simulations revealed that Amblyomin-X is structurally stable and the naturally unfolded regions as well as the presence of three disulfide bridges in its Kunitz-type domain seem to sustain its inhibitory activity. Regarding the electrostatic potential mapping on the Kunitz-type region, the pattern of charged residues was not quite the same in comparison to human TFPI-1 and TFPI-2, pointing out there might be distinct functional and structural features, which are going to be experimentally exploited. (AU)

Processo FAPESP: 10/52669-3 - Avaliação do mecanismo de ação pró-apoptótica do Amblyomin-X
Beneficiário:Ana Marisa Chudzinski-Tavassi
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 11/21912-2 - Avaliação do mecanismo de ação pró-apoptótica do Amblyomin-X
Beneficiário:Kerly Fernanda Mesquita Pasqualoto
Linha de fomento: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico