Trypanosoma cruzi is the aetiological agent of Chagas' disease, a chronic infection that affects millions in Central and South America. Proteolytic enzymes are involved in the development and progression of this disease and two metallocarboxypeptidases, isolated from T. cruzi CL Brener clone, have recently been characterized: TcMCP-1 and TcMCP-2. Although both are cytosolic and closely related in sequence, they display different temporary expression patterns and substrate preferences. TcMCP-1 removes basic C-terminal residues, whereas TcMCP-2 prefers hydrophobic/aromatic residues. Here we report the three-dimensional structure of TcMCP-1. It resembles an elongated cowry, with a long, deep, narrow active-site cleft mimicking the aperture. It has an N-terminal dimerization subdomain, involved in a homodimeric catalytically active quaternary structure arrangement, and a proteolytic subdomain partitioned by the cleft into an upper and a lower moiety. The cleft accommodates a catalytic metal ion, most likely a cobalt, which is co-ordinated by residues included in a characteristic zinc-binding sequence, HEXXH and a downstream glutamate. The structure of TcMCP-1 shows strong topological similarity with archaeal, bacterial and mammalian metallopeptidases including angiotensin-converting enzyme, neurolysin and thimet oligopeptidase. A crucial residue for shaping the S(1') pocket in TcMCP-1, Met-304, was mutated to the respective residue in TcMCP-2, an arginine, leading to a TcMCP-1 variant with TcMCP-2 specificity. The present studies pave the way for a better understanding of a potential target in Chagas' disease at the molecular level and provide a template for the design of novel therapeutic approaches.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1111/j.1365-2958.2008.06444.x | DOI Listing |
Front Pharmacol
January 2025
Instituto de Farmacia, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile.
This research was designed to investigate the metabolite profiling, phenolics content, and the trypanocidal, nematicidal, antibacterial, antifungal, and free radical scavenging properties of Motyka. The air-dried material was extracted successively with dichloromethane and methanol (UlMeOH). Two phases were obtained from the extract with dichloromethane, one soluble in methanol (UlDCM-s) and the other insoluble (UlDCM-i).
View Article and Find Full Text PDFInt J Parasitol
January 2025
Grupo de Enfermedades Infecciosas Facultad de Ciencias Pontificia Universidad Javeriana Bogotá Colombia. Electronic address:
Bats play crucial roles in various ecosystems including caves. Although the presence of trypanosomatid species in bats has been documented in Colombia, their diversity in cave-dwelling bats remains unclear. This study aimed to characterize the frequency and diversity of protists from the family Trypanosomatidae circulating in bats from the Macaregua cave ecosystem in Santander, Colombia.
View Article and Find Full Text PDFJ Exp Zool A Ecol Integr Physiol
January 2025
Laboratorio de Ecología de Enfermedades, Instituto de Ciencias Veterinarias del Litoral (ICIVET LITORAL), Universidad Nacional del Litoral - CONICET, Santa Fe, Santa Fe, Argentina.
To overcome infection, hosts employ two defense strategies: resistance (which limits pathogen fitness), and tolerance (which reduces infection damage). These strategies may be influenced by environmental challenges such as food shortage, social conflict, and co-infections. Here, our objective was to assess defense strategies in rats infected with Trichinella spiralis and/or Trypanosoma cruzi under environmental challenges.
View Article and Find Full Text PDFEcohealth
January 2025
Department of Agricultural and Environmental Sciences, State University of Santa Cruz, Direction of the University: Campus Soane Nazaré de Andrade, Rod. Jorge Amado, Km 16 - Salobrinho, Ilhéus, Bahia, 45662-900, Brazil.
The black rat Rattus rattus is an exotic and synanthropic rodent prominent in Brazil and with high adaptation to urban areas. The species have an omnivorous diet feed on human food resources, potentially becoming infected and spreading infectious agents that cause zoonoses such as leptospirosis, leishmaniosis, Chagas disease, and toxoplasmosis, which are significant public health concerns in the country. We analyzed the epidemiologic profile of R.
View Article and Find Full Text PDFFront Parasitol
September 2024
Centro de Cálculo Científico de la Universidad de Los Andes (CeCalCULA), Universidad de Los Andes (ULA), Mérida, Venezuela.
Artemisinin-based treatments (ACTs) are the first therapy currently used to treat malaria produced by . However, in recent years, increasing evidence shows that some strains of are less susceptible to ACT in the Southeast Asian region. A data reanalysis of several omics approaches currently available about parasites of that have some degree of resistance to ACT was carried out.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!