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Project
A Combined Experimental and Theoretical Approach towards Sulfenylation in the Peroxiredoxin AhpE of M. tuberculosis: Unraveling its Redox Chemistry (FWOAL622)
Every 20 seconds a person dies from tuberculosis (TB), which sums up to over 2 million deaths each year. Therefore, the World Health Organization as well as the European Commission consider fighting TB as one of the main goals for the coming years.
The agent causing TB is Mycobacterium tuberculosis (Mtb). Mtb infect, reside and multiply in alveolar macrophages. Mtb causes the formation of granulomas, where this pathogen is exposed to reactive oxygen species (ROS) and reactive nitrogen species, which generate a toxic environment aimed to kill the bacteria. Mtb engages advanced strategies to fight oxidative stress. One of the key enzymes in the defence mechanism of Mtb is a one-cys peroxiredoxin AhpE. AhpE scavenges ROS by its active site cysteine. In this process, the cysteine is oxidized to the sulfenic acid. We will study how the enzymatic environment influences the cysteine sulfenylation, and the electron-transfer pathways in which AhpE is involved. We will use a multidisciplinary approach involving kinetic experiments, and theoretical calculations to establish the rate determining structural environment for cysteine sulfenylation. The moment we understand the details of this ROS-scavenging enzyme, we might start to think about strategies to interfere with this defence mechanism of Mtb.
The agent causing TB is Mycobacterium tuberculosis (Mtb). Mtb infect, reside and multiply in alveolar macrophages. Mtb causes the formation of granulomas, where this pathogen is exposed to reactive oxygen species (ROS) and reactive nitrogen species, which generate a toxic environment aimed to kill the bacteria. Mtb engages advanced strategies to fight oxidative stress. One of the key enzymes in the defence mechanism of Mtb is a one-cys peroxiredoxin AhpE. AhpE scavenges ROS by its active site cysteine. In this process, the cysteine is oxidized to the sulfenic acid. We will study how the enzymatic environment influences the cysteine sulfenylation, and the electron-transfer pathways in which AhpE is involved. We will use a multidisciplinary approach involving kinetic experiments, and theoretical calculations to establish the rate determining structural environment for cysteine sulfenylation. The moment we understand the details of this ROS-scavenging enzyme, we might start to think about strategies to interfere with this defence mechanism of Mtb.
Date:1 Jan 2012 → 31 Dec 2015
Keywords:Chemistry
Disciplines:Chemical sciences