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Title: Revealing a novel Otubain-Like Enzyme from Leishmania infantum with deubiquitinating activity toward K48-linked substrate
Authors: Azevedo, Clênia dos Santos
Guido, Bruna Cândido
Pereira, Jhonata L.
Nolasco, Diego O.
Corrêa, Rafael
Magalhães, Kelly Grace
Motta, Flávia Nader
Santana, Jaime Martins de
Grellier, Philippe
Bastos, Izabela Marques Dourado
Assunto:: Enzimas
Leishmania
Leishmaniose - tratamento
Issue Date: 23-Mar-2017
Publisher: Frontiers in Chemistry
Citation: AZEVEDO, Clênia dos Santos et al. Revealing a novel Otubain-Like Enzyme from Leishmania infantum with deubiquitinating activity toward K48-linked substrate. Frontiers in Chemistry, v. 5, Artile 13, 23 mar. 2017. Disponível em: <http://journal.frontiersin.org/article/10.3389/fchem.2017.00013/full>. Acesso em: 21 jun. 2017. doi: http://journal.frontiersin.org/article/10.3389/fchem.2017.00013/full.
Abstract: Deubiquitinating enzymes (DUBs) play an important role in regulating a variety of eukaryotic processes. In this context, exploring the role of deubiquitination in Leishmania infantum could be a promising alternative to search new therapeutic targets for leishmaniasis. Here we present the first characterization of a DUB from L. infantum, otubain (OtuLi), and its localization within parasite. The recombinant OtuLi (rOtuLi) showed improved activity on lysine 48 (K48)-linked over K63-linked tetra-ubiquitin (Ub) and site-directed mutations on amino acids close to the catalytic site (F82) or involved in Ub interaction (L265 and F182) caused structural changes as shown by molecular dynamics, resulting in a reduction or loss of enzyme activity, respectively. Furthermore, rOtuLi stimulates lipid droplet biogenesis (an inflammatory marker) and induces IL-6 and TNF-a secretion in peritoneal macrophages, both proinflammatory cytokines. Our findings suggest that OtuLi is a cytoplasmic enzyme with K48-linked substrate specificity that could play a part in proinflammatory response in stimulated murine macrophages.
Licença:: Copyright © 2017 Azevedo, Guido, Pereira, Nolasco, Corrêa, Magalhães, Motta, Santana, Grellier and Bastos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
DOI: https://dx.doi.org/10.3389/fchem.2017.00013
Appears in Collections:CEL - Artigos publicados em periódicos

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