Structural characterization of enzymes involved in riboflavin biosynthesis in Brucella for the rational design of drugs against human brucellosis (Conferencia en Simposio de Microbiología)

SEBASTIÁN KLINKE; MARÍA I. SERER; MARIELA DEL C. CARRICA; HERNÁN R. BONOMI; MARÍA L. CERUTTI; FERNANDO A. GOLDBAUM

Rosario

Congreso; LIX Reunión Anual de la Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular (SAIB); 2023

Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular (SAIB)

The pathogenic bacterium Brucella abortus, a Gram-negative microorganism that causes the severe zoonotic disease brucellosis, relies exclusively on its endogenous synthesis of riboflavin (vitamin B2). The absence of this metabolic pathway in mammals highlights the enzymes involved in the biosynthesis of this vitamin as attractive targets with therapeutic potential. We have demonstrated that the deletion of certain genes that encode for enzymes of this pathway results in a significantly reduced virulence phenotype, with B. abortus being rapidly eliminated by the host in cellular and animal infection models. Our laboratory has a strong background in X-ray crystallography for the determination of the three-dimensional structure of macromolecules. By means of this technique, we have thoroughly characterized three of the enzymes of the riboflavin pathway in B. abortus: Lumazine synthase, 5-Amino-6-ribosylamino-2,4(1H,3H)-pyrimidinedione 5'-phosphate reductase, and Riboflavin synthase. Based on these achievements, this project aims at the rational design of drugs against human brucellosis by the combination of high-throughput screening and structure-based drug design.