Mycobacterium tuberculosis Prolyl Oligopeptidase Induces In vitro Secretion of Proinflammatory Cytokines by Peritoneal Macrophages
Autor: | Hugo de Almeida, Kelly Grace Magalhães, Andre F. Correa, Brina Portugal, Flávia Nader Motta, Diego O. Nolasco, Ana L. V. Atta, Jaime M. Santana, Izabela Marques Dourado Bastos, Francisco D. Vieira |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Microbiology (medical) Proteases Tuberculosis serine protease medicine.medical_treatment Oligopeptidase Microbiology Proinflammatory cytokine Mycobacterium tuberculosis 03 medical and health sciences 0302 clinical medicine Immune system medicine Original Research Serine protease Protease biology Mycobacterium tuberculosis protease molecular dynamic fluorescence spectroscopy medicine.disease biology.organism_classification 030104 developmental biology tuberculosis prolyl oligopeptidase proinflammatory cytokines biology.protein 030217 neurology & neurosurgery |
Zdroj: | Frontiers in Microbiology |
ISSN: | 1664-302X |
Popis: | Tuberculosis (TB) is a disease that leads to death over 1 million people per year worldwide and the biological mediators of this pathology are poorly established, preventing the implementation of effective therapies to improve outcomes in TB. Host–bacterium interaction is a key step to TB establishment and the proteases produced by these microorganisms seem to facilitate bacteria invasion, migration and host immune response evasion. We presented, for the first time, the identification, biochemical characterization, molecular dynamics (MDs) and immunomodulatory properties of a prolyl oligopeptidase (POP) from Mycobacterium tuberculosis (POPMt). POP is a serine protease that hydrolyzes substrates with high specificity for proline residues and has already been characterized as virulence factor in infectious diseases. POPMt reveals catalytic activity upon N-Suc-Gly-Pro-Leu-Gly-Pro-AMC, a recognized POP substrate, with optimal activity at pH 7.5 and 37°C. The enzyme presents KM and Kcat/KM values of 108 μM and 21.838 mM-1 s-1, respectively. MDs showed that POPMt structure is similar to that of others POPs, which consists of a cylindrical architecture divided into an α/β hydrolase catalytic domain and a β-propeller domain. Finally, POPMt was capable of triggering in vitro secretion of proinflammatory cytokines by peritoneal macrophages, an event dependent on POPMt intact structure. Our data suggests that POPMt may contribute to an inflammatory response during M. tuberculosis infection. |
Databáze: | OpenAIRE |
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