Bioinorganic Chemistry of Metalloenzymes

In our Laboratory we study metalloenzymes (containing transition metals) with diverse functions, at the molecular level;  a  particular emphasis is given to those involved in combating oxidative and nitrosative stresses, namely from microbial pathogens.

The presence of oxygen in the atmosphere poses a challenge to living systems. On the one hand, oxygen is essential for aerobic life, allowing the generation of high energy yields through respiration and oxidative phosphorylation. On the other hand, the non controlled reduction of oxygen to water, in consecutive one electron reactions (O₂/O₂^-./H₂O₂/OH^./H₂O), leads to the formation of Reactive Oxygen Species (ROS) which are deleterious to the cells. This fact compels both anaerobic and aerobic organisms that encounter ROS, to have mechanisms to detoxify them. The source of ROS can result from permanent or transient exposures to oxygen and/or to the immune system of higher organisms that use ROS as weapons against invading pathogens; this occurs through the so called oxidative burst generated by neutrophils/macrophages. Those cells also generate NO that leads to the damage of key cellular components. Therefore it is particularly important to understand the response of microbes to oxygen and NO as well as derived reactive oxygen and nitrogen species, as part of their strategies to overcome the immune system. In our laboratory we use a wide range of methodologies, both in-house and through National or International collaborations to study the most recently discovered metalloenzymes involved in those processes, as well as the respective electron transfer chains, that involve NAD(P)H oxidoreductases and rubredoxin or rubredoxin-like proteins/enzymes.

Overview of the metalloenzymes involved in defence systems against ROS. Superoxide reductases, peroxidases and flavodiiron proteins are our main subject of study		Some defence systems used by pathogens against superoxide and NO. Superoxide and NO are toxic radicals produced by macrophages to kill microorganisms upon infections. However, some pathogens have developed strategies to defend themselves against this attack, by using enzymes that eliminate these toxic species, and thus being able to survive