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The Trypanosoma cruzi virulence factor oligopeptidase B (OPBTc) assembles into an active and stable dimer.

Abstract
Oligopeptidase B, a processing enzyme of the prolyl oligopeptidase family, is considered as an important virulence factor in trypanosomiasis. Trypanosoma cruzi oligopeptidase B (OPBTc) is involved in host cell invasion by generating a Ca(2+)-agonist necessary for recruitment and fusion of host lysosomes at the site of parasite attachment. The underlying mechanism remains unknown and further structural and functional characterization of OPBTc may help clarify its physiological function and lead to the development of new therapeutic molecules to treat Chagas disease. In the present work, size exclusion chromatography and analytical ultracentrifugation experiments demonstrate that OPBTc is a dimer in solution, an association salt and pH-resistant and independent of intermolecular disulfide bonds. The enzyme retains its dimeric structure and is fully active up to 42°C. OPBTc is inactivated and its tertiary, but not secondary, structure is disrupted at higher temperatures, as monitored by circular dichroism and fluorescence spectroscopy. It has a highly stable secondary structure over a broad range of pH, undergoes subtle tertiary structure changes at low pH and is less stable under moderate ionic strength conditions. These results bring new insights into the structural properties of OPBTc, contributing to future studies on the rational design of OPBTc inhibitors as a promising strategy for Chagas disease chemotherapy.
AuthorsFlávia Nader Motta, Izabela M D Bastos, Eric Faudry, Christine Ebel, Meire M Lima, David Neves, Michel Ragno, João Alexandre R G Barbosa, Sônia Maria de Freitas, Jaime Martins Santana
JournalPloS one (PLoS One) Vol. 7 Issue 1 Pg. e30431 ( 2012) ISSN: 1932-6203 [Electronic] United States
PMID22276197 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Protozoan Proteins
  • Virulence Factors
  • Serine Endopeptidases
  • oligopeptidase B
Topics
  • Chromatography, Gel
  • Circular Dichroism
  • Protein Multimerization
  • Protozoan Proteins (chemistry, metabolism)
  • Serine Endopeptidases (chemistry, metabolism)
  • Spectrometry, Fluorescence
  • Temperature
  • Trypanosoma cruzi (metabolism)
  • Virulence Factors (chemistry, metabolism)

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