Scientific discoveries are very often the result of a lucky break. Many researchers can attest to this: their research sometimes leads them on a merry dance. Indeed, very often while working on their chosen subject, it happens that new avenues open up and lead to unexpected discoveries. Professor Lucien Bettendorff, Director of the GIGA Bioenergetics and cerebral Excitability Research Unit, and David Delvaux, a doctoral student in the same unit have recently had such an experience.

For more than twenty-five years, Lucien Bettendorff has been studying thiamine, a molecule that is better known as vitamin B1. It plays a key role in the primary metabolism of all living organisms. Up to the present, four derivatives of thiamine are known: monophosphate, diphosphate and thiamine triphosphate, which contain one, two and three groups of phosphates respectively. In 2007, while they were working on thiamine triphosphate in bacteria, Lucien Bettendorff and his team discovered a fourth derivative of vitamin B1 : adenosine thiamine triphosphate (see article « Vitamins have not yet revealed all their secrets »).

Even if scientists think that these derivatives play a role in energy metabolism and that they are probably involved in the mechanisms linked to neurodegenerative diseases, the functions of these compounds remain largely unknown. What are their roles in cellular bioenergetics ? Could it be possible to manipulate the metabolism of phosphorylated derivatives of thiamine to counter the adverse effects of cellular stress and neurodegeneration? There are some of the many questions that Lucien Bettendorff and his colleagues are trying to find answers to.

The superfamily of CYTH proteins under the microscope.

Apart from these thiamine derivatives, the researchers from Liège are also interested in enzymes which hydrolize these derivatives, such as the 25-kDa thiamine triphosphatase. This enzyme, which belongs to the CYTH superfamily of proteins, specifically hydrolyses thiamine triphosphate in mammals. It is this superfamily of proteins that David Delvaux is particularly interested in, in the context of his thesis. Indeed, he has closely studied the catalytic mechanism and the structure of proteins of the CYTH superfamily. During the course of his research, David Delvaux has compared a CYTH protein that is found in the Nitrosomonas europea bacteria and which has been named NeuTTM and the 25-kDa thiamine triphosphatase. The scientists realized that these two enzymes had very similar structures. « We then asked ourselves if NeuTTM could be a bacterial thiamine triphosphatase », explains Lucien Bettendorff.

David Delvaux, Mamidanna R.V.S. Murty, Valérie Gabelica, Bernard Lakaye, Vladimir V. Lunin, Tatiana Skarina, Olena Onopriyenko, Gregory Kohn, Pierre Wins, Edwin De Pauw and Lucien Bettendorff. A specific inorganic triphosphatase from Nitrosomonas europaea: structure and catalytic mechanism J. Biol. Chem. 2011, 286: 34023-34035.