CYSTEINE AS A PEROXIDATIC AGENT: AQUEOUS SOLUTION vs. PROTEIN ENVIRONMENT

ARI ZEIDA; MARIANO CAMILO GONZÁLEZ LEBRERO; MADIA TRUJILLO; RAFAEL RADI; DARIO A. ESTRIN

Búzios

Congreso; II Latin American Federation of Biophysical Societies Congress; 2012

Latin American Federation of Biophysical Societies

Oxidation of cellular thiol containing compounds such as glutathione and protein Cys residues by reactive oxygen species is considered to play important roles in a wide array of biological processes including signal transduction, regulation of the activity of enzymes, protein channels, transcription factors and antioxidant responses. Peroxides such as hydrogen peroxide (H2O2), peroxynitrite and fatty acid hydroperoxides are produced in many cell types as a response to a variety of extracellular stimuli and could work as ubiquitous intracellular messengers. Particularly, the two-electron oxidation of reactive protein Cys by peroxides is a key event during redox signaling and regulation. Though this reaction has been extensively studied, the detailed mechanism remains poorly understood. Peroxiredoxins are thiol-dependent enzymes that reduce different peroxides several orders of magnitude faster than other thiol-containing compounds such as free cysteine, by catalytic mechanisms that are starting to be unraveled, hence structure-dynamical studies have became very significant. In particular, the alkyl hydroperoxide reductase E (AhpE), the one-cysteine peroxiredoxin from Mycobacterium tuberculosis, reduces fatty acid hydroperoxides and peroxynitrite much faster than H2O2. In this contribution, we studied the molecular basis of Cys oxidation by different substrates, both in aqueous solution and within MtAhpE context, via a combination of experimental and theoretical (MD and QM-MM simulations) approaches. This strategy alloud us to get relevant kinetical and thermodynamical information, together with the evaluation and comparison of the microscopic environment influence.