Seminario impartido por Cele Abad-Zapatero, del Institute for Tuberculosis Research, University of Illinois, Chicago
Natural products isolated from a wide variety of sources continue to be the inspiration to design novel antibiotic leads to address the worldwide concern over antibiotic resistance. Mycobacterium tuberculosis continues to be a persistent pathogen in human populations and a grave cause of mortality and morbidity due to the emergence of resistant strains in the human population. Previous screening work had isolated two potent cyclopeptides as anti-TB agents from actinomycetes sources, Rufomycin and Ecumicin, that were later characterized as specific inhibitors of the protein homeostatic machinery oligomeric complex ClpC1/P1/P2. Our group has been able to co-crystallize complexes of these cyclopeptides with the N-terminal domain of the ClpC1 element (ClpC1-NTD) of the three-layered aggregate and characterize their mode of binding to their M. tuberculosis target. The results of the crystallographic analyses of these complexes will be presented highlighting the critical interactions, oligomeric aggregation with the target protein and the implications for current drug discovery leads.
Fecha del seminario: 21/06/2024 12:00
Lugar del seminario: salón de actos IQF
Ponente del seminario: Celerino Abad-Zapatero
