Understanding the molecular basis of oxidizing substrate specificity in peroxiredoxins: the case of AhpE from Mycobacterium tuberculosis

MARCELO REYES; ARI ZEIDA; LICHTIG, PABLO; MARTIN HUGO; DIEGO SEBASTIAN VAZQUEZ; JAVIER SANTOS; FRANCISCO LUIS GONZÁLEZ FLECHA; RADI, RAFAEL; ESTRIN, DARÍO; TRUJILLO, MADIA

Foz do Iguaçu, Brazil

Congreso; 23rd Congress of the IUMBM and 44th Annual Meeting of the Brazilian Society for Biochemistry and Molecular Biology; 2015

International Union for Biochemistry and Molecular Biology & Brazilian Society for Biochemistry and Molecular Biology

Peroxiredoxins (Prxs) are Cys-dependent peroxidases that reduce different hydroperoxides playing a key role in reactive oxidizing species detoxification and redox signaling. Among them, alkyl hydroperoxide reductase E (AhpE) represents a Prx subfamily comprising Mycobacterium tuberculosis AhpE (MtAhpE) and AhpE-like proteins from bacteria and archaea. We reported that MtAhpE reacts ~104 times faster with arachidonic-derived hydroperoxide (15-HpETE) than H2O2, suggesting this surprisingly high reactivity could be due to the presence of a hydrophobic groove at a dimer interface. Herein, we use a combined experimental and computational approach to understand the molecular basis of this selectivity towards this hydroperoxide substrates.