Abstract: Inhibition of the biosynthesis of tetrahydrofolate (THF) has long been a focus in the treatment of both cancer and infectious disease. Dihydrofolate reductase (DHFR), which catalyses the last step, is one of the most thoroughly explored targets of this pathway, but there are no DHFR inhibitors used for tuberculosis treatment. In this talk we will show a structural, site-directed mutagenesis and calorimetric analysis of Mycobacterium tuberculosis DHFR (MtDHFR) in complex with classical DHFR inhibitors. We will show insights into the weak inhibition of MtDHFR by trimethoprim and other antifolate drugs, such as pyrimethamine and cycloguanil. We will discuss about the movements of loops and domains of the enzyme with new insights in the evaluative process of the enzyme.  Possible strategies in drug design for new series of DHFR inhibitors that are independent of the interaction with the co-factor will also be shown.

Speaker: Dr. Marcio Vinícius Bertacine Dias (LNBio)

21th October at 8:30 am

Room 69 – LNBio
Campus – Centro Nacional de Pesquisa em Energia e Materiais – CNPEM
Rua Giuseppe M. Scolfaro, 10.000 – Guará
Tel: (19) 3512-1010