SCAN:Reductive elimination of Reactive Oxygen Species: Structural and Functional Insights

ITQB SCAN Seminar

Title: Reductive elimination of Reactive Oxygen Species: Structural and Functional Insights

Speaker: Miguel Sepúlveda Teixeira

From: Head of Metalloenzymes and Molecular Bioenergetics Laboratory

Abstract:

Living cells are, even if only transiently, exposed to dioxygen, with the resulting production of Reactive Oxygen Species (ROS), namely the superoxide anion and hydrogen peroxide. A major source for ROS is the Oxidative Burst produced by the innate immune system, as a weapon against invading pathogens. To counteract the deleterious effects of ROS, and counteract the immune system, organisms evolved specialized enzymatic systems, mainly based on disproportionation mechanisms: superoxide dismutases (dismutation of the superoxide anion) and catalases (dismutation of hydrogen peroxide). However, these systems are not universal, and in particular in anaerobic bacteria and archaea, as well as in a few eukaryotic protozoa, completely different systems have been discovered, based on the reductive elimination of ROS. One of these systems, which will be addressed in this lecture, are the superoxide reductases, spread among anaerobic and facultative microorganisms, from the three life kingdoms. These enzymes share the same unique catalytic site, an iron-ion bound to four histidines and a cysteine, in a domain organized in a seven-stranded (3+4 sheet) β-barrel that adopts an immunoglobulin-like fold. The reaction mechanism has been elucidated by a combination of pulse radiolysis, and electronic and Resonance Raman spectroscopies, of wild type and site directed mutants, and by determination of 3D crystallographic structures. In the reduced form, the SORs react with the superoxide anion with a diffusion-limited second order rate constant of ~109 M-1s-1, forming a ferric hydroperoxide species. Subsequently this transient may decay to an iron-hydroxide form or directly to the ferric resting form. The reduced form is rapidly re-formed by receiving electrons from rubredoxins, with a rate constant faster than 107 M-1s-1. Overall, the superoxide reduction process apeears as efficient as the canonical dismuatation one, performed by the superoxide dismutases.