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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Kinetic characterization of a novel cysteine peptidase from the protozoan Babesia bovis, a potential target for drug design

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Author(s):
Lu, Stephen [1] ; Ascencio, Mariano E. [2] ; Torquato, Ricardo J. S. [1] ; Florin-Christensen, Monica [2] ; Tanaka, Aparecida S. [1, 3]
Total Authors: 5
Affiliation:
[1] Univ Fed Sao Paulo UNIFESP, Escola Paulista Med, Dept Biochem, Rua 3 Maio 100, BR-04044020 Sao Paulo, SP - Brazil
[2] INTA Castelar, Ctr Invest Ciencias Ve & Agron CICVyA, Inst Patobiol Vet, Los Reseros & Nicolas Repetto S-N, RA-1686 Hurlingham - Argentina
[3] Inst Nacl Ciencia & Tecnol Entomol INCT EM, Rio De Janeiro - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Biochimie; v. 179, p. 127-134, DEC 2020.
Web of Science Citations: 0
Abstract

C1A cysteine peptidases have been shown to play an important role during apicomplexan invasion and egress of host red blood cells (RBCs) and therefore have been exploited as targets for drug development, in which peptidase specificity is deterministic. Babesia bovis genome is currently available and from the 17 putative cysteine peptidases annotated four belong to the C1A subfamily. In this study, we describe the biochemical characterization of a C1A cysteine peptidase, named here BbCp (B. bovis cysteine peptidase) and evaluate its possible participation in the parasite asexual cycle in host RBCs. The recombinant protein was obtained in bacterial inclusion bodies and after a refolding process, presented typical kinetic features of the cysteine peptidase family, enhanced activity in the presence of a reducing agent, optimum pH between 6.5 and 7.0 and was inhibited by cystatins from R. microplus. Moreover, rBbCp substrate specificity evaluation using a peptide phage display library showed a preference for Val > Leu > Phe. Finally, antibodies anti-rBbCp were able to interfere with B. bovis growth in vitro, which highlights the BbCp as a potential target for drug design. (C) 2020 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved. (AU)

FAPESP's process: 15/09268-1 - Characterization of two proteases from Babesia bovis parasite: Importance in the host infections.
Grantee:Stephen Lu
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 17/25609-9 - Characterization of two proteases from Babesia bovis parasite and their relevance in host infection.
Grantee:Stephen Lu
Support type: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 12/03657-8 - Inhibitor and proteases of ectoparasites: relationship of structure-function and identification of the role of these molecules in the interaction of diseases vector e their etiological agents
Grantee:Aparecida Sadae Tanaka
Support type: Research Projects - Thematic Grants