Structural modelling and thermostability of a serine protease inhibitor belonging to the Kunitz-BPTI family from the Rhipicephalus microplus tick

Autor(es)

Bomediano Camillo, Livia de Moraes ^[1] ; Ferreira, Graziele Cristina ^[1] ; Alves Duran, Adriana Feliciano ^[1] ; Santos da Silva, Flavia Ribeiro ^[1] ; Garcia, Wanius ^[2] ; Scott, Ana Ligia ^[3] ; Sasaki, Sergio Daishi ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Sao Bernardo Do Campo, SP - Brazil

^[2] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Santo Andre, SP - Brazil

^[3] Univ Fed ABC, Ctr Matemat Comp & Cognicao, Santo Andre, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Biochimie; v. 181, p. 226-233, FEB 2021.
• Citações Web of Science: 0

Resumo

rBmTI-A is a recombinant serine protease inhibitor that belongs to the Kunitz-BPTI family and that was cloned from Rhipicephalus microplus tick. rBmTI-A has inhibitory activities on bovine trypsin, human plasma kallikrein, human neutrophil elastase and plasmin with dissociation constants in nM range. It is characterized by two inhibitory domains and each domain presents six cysteines that form three disulfide bonds, which contribute to the high stability of its structure. Previous studies suggest that serine protease inhibitor rBmTI-A has a protective potential against pulmonary emphysema in mice and anti-inflammatory potential. Besides that, rBmTI-A presented a potent inhibitory activity against in vitro vessel formation. In this study, the tertiary structure of rBmTI-A was modeled. The structure stabilization was evaluated by molecular dynamics analysis. Circular dichroism spectroscopy data corroborated the secondary structure found by the homology modelling. Also, in circular dichroism data it was shown a thermostability of rBmTI-A until approximately 70 degrees C, corroborated by inhibitory assays toward trypsin. (C) 2020 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved. (AU)

• Processo FAPESP: 11/07001-7 - Estudos da atividade de inibidores de serinoproteases originários do carrapato Rhipicephalus Boophilus microplus em modelo de enfisema pulmonar em camundongos e caracterização molecular das atividades de serinoproteases presentes no modelo
• Beneficiário: Sergio Daishi Sasaki
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/19077-4 - Dinâmica estrutural e mecanismos moleculares envolvidos na agregação da alfa-sinucleína
• Beneficiário: Ana Lígia Barbour Scott
• Modalidade de apoio: Bolsas no Exterior - Pesquisa
• Processo FAPESP: 18/11874-5 - Inibidores de serinoproteases em células pulmonares e em enfisema pulmonar
• Beneficiário: Sergio Daishi Sasaki
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/17275-3 - Estudos do modo de ação de duas mono-oxigenases líticas de polissacarídeos de inseto (ordem isoptera): estrutura molecular, química bioinorgânica e aplicações biotecnológicas
• Beneficiário: Wanius José Garcia da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular