IIT Biologists Determine the Molecular Mechanisms of Enzyme Action in Cholera and Related Diseases

Illinois Institute of Technology biologists have described the operation at the molecular level of a key enzyme associated with cholera-causing bacteria.

Karina Tuz, research assistant professor of biology, and Oscar Juarez, assistant professor of biology, and their teammates determined the molecular mechanism of the main sodium pump of the bacteria that produces severe gastrointestinal disease to millions of people in developing countries. An article describing their work, “The kinetic reaction mechanism of Vibrio cholerae sodium-dependent NADH Dehydrogenase,” was a paper of the week in the prestigious Journal of Biological Chemistry. JBC also profiled Tuz and interviewed Juarez for a podcast.

Vibrio cholerae and a number of other pathogenic bacteria rely on a sodium-dependent NADH dehydrogenase (Na+-NQR). Na+-NQR is the first enzyme in the respiratory chain, and its activity is essential for drug elimination and virulence factor secretion. However, its mechanism of action had not been clear.

With the use of enzyme kinetics analysis, Tuz and Juarez were able to describe the molecular events, down to the movement of electrons, that drive the reaction of this enzyme. The data indicate that the enzyme undergoes a series of conformational changes during its catalytic cycle and helps understand the mechanism used by the enzyme to transport electrons and pump sodium.

The sodium-dependent NADH dehydrogenase represents an ideal target for drug design, since it is an essential metabolic step that is involved in the infection cycle of different pathogens and the genes coding for this complex are absent in the human genome. The data found in this report is essential to the Juarez team’s efforts to produce new antibiotics, because it allows for the identification of structures that can be susceptible to drugs.

Only two percent of the papers accepted by JBC are highlighted as papers of the week, based on their significance and impact.

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Oscar Juarez and Karina Tuz