Biological aspects of thiols: protein structure, antioxidant defense, cell signaling and redox states

Abstract

The classical concept of oxidative stress is "a disturbance in the pro-oxidant-antioxidant balance in favor of the former". However, the accumulation of data indicates that a more useful definition is a "disruption of redox signaling and control" [...]. The tri-peptide glutathione plays a central role in the redox homeostasis, but there are also other thiols that participate in redox signaling. These thiols that make part of redox pairs (RSH/RSSR) are enzymes that contain reactive cysteines (such as thioredoxins, glutaredoxins and peroxiredoxins) and are widely distributed. In this project, we propose to characterize structurally and functionally several thiol systems, especially those derived from the model organism, Saccharomyces cerevisiae. We have already elucidated the structures of several proteins that compose these systems and now o intend: 1) to elucidate novel structures; 2) continue to make functional-structural correlations and 3) determined structure of protein complexes. Among these studies, we intend to investigate in further details a new antioxidant pathway: the reduction of 1-Cys peroxiredoxins by ascorbate (vitamin C). Our studies [...] changed the "thiols specific antioxidant paradigm" of these thiol-disulfide oxido¬reductases and opened the perspective that these low molecular weight compounds can interfere in the redox states of several thiol systems and, consequently, in redox signaling. We also intend to continue our characterization of antioxidant systems from Xylella fastidiosa. Previously, we elucidated the first structure of a protein (Ohr) from Xylella fastidiosa [...]. Since Ohr is exclusively present in bacteria, this protein may represent a promising target for drug design. Other antioxidant systems from Xylella fastidiosa are also currently being analyzed. (AU)