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PerR, a hydrogen peroxide sensor

We have shown [collaboration] a radically new mechanism for detection by a protein of the oxidative stress induced by hydrogen peroxide (H2O2).

Published on 16 January 2009

An unavoidable consequence of aerobic life is the production of reactive oxygen species (ROS) such as superoxide anions, hydrogen peroxide and hydroxyl radicals, which are capable of damaging numerous cellular components, including nucleic acids, proteins and lipids. In collaboration with DSV, a new mechanism by which PerR proteins detect oxidative stress induced by hydrogen peroxide has been discovered.

To counteract the effect of oxidative stress, organisms have developed several tools to detect and destroy ROS. In some bacteria, a protein named PerR is involved in the regulation of these defense mechanisms.

PerR impedes the synthesis of protective enzymes by binding to a specific DNA strand [A]. PerR thus prevents the cell from expending unnecessary energy by synthesizing too much defense proteins in the absence of threat. But, in the presence of hydrogen peroxide H2O2 [B], PerR is oxidized [C] and binding affinity to DNA is significantly reduced. Released DNA [D] initiates the chain of the cell defenses against oxidative stress.

In general, the oxidation of proteins sensitive to ROS occurs at a particular amino acid, cysteine, which contains easily oxidized thiol groups. In the case of PerR, it has been shown that H2O2 oxide another amino acid, histidine. Identification and quantification of histidine in oxidized PerR has been performed in the SCIB group by liquid phase chromatography coupled to tandem mass spectrometry. The work has unambiguously demonstrated, using complementary approaches, that histidine oxidation is required to activate PerR in response to oxidative stress. Oxidation prevents DNA binding. Common to several strains of bacteria, but absent in humans, PerR may well become an attractive target for developing new antibacterial agents.

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