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Joint research into an enzyme that causes genetic diseases

Researchers from CIC bioGUNE's Structural Biology Unit and Columbia University (New York) have conducted a joint research project, published in the prestigious scientific journal Structure, to gain in-depth knowledge of the structure of pyruvate carboxylase when it is in solution (in the "natural" state).

Pyruvate carboxylase is a metabolic enzyme that plays a fundamental role in the metabolism of fatty acids (the components of fats) and sugars. When its function is not adequately performed (for example, when mutations in the gene arise) diverse metabolic diseases of genetic origin are triggered, amongst them lactic acidaemia, hypoglycaemia, and psycho-motor retardation. At the same time, being at a metabolic crossroads, pyruvate carboxylase is potentially a target in obesity and diabetes treatments.

The paper presents the enzyme's structure under physiological conditions for the first time, and reveals which of the previous models is the correct one.

Mikel Valle, a researcher from CIC bioGUNE's Structural Biology Unit explains that This is the start of a highly ambitious study which is being carried out at CIC bioGUNE and which aims to discover the functioning of pyruvate carboxylase. This they shall achieve by observing its structure throughout its functional cycle, in the hope of discovering its structure in each of the steps it follows during its functioning.

The project has been conducted together with the New York Structural Biology Center (NYSBC). Set up in 2002, this Center uses the most advanced Molecular Magnetic Resonance imaging, Electron Microscopy, and X-ray crystallography equipment (as does CIC bioGUNE's Structural Biology Unit). In this joint research project, the NYSBC took charge of the X-ray crystallography part, while CIC bioGUNE's Structural Biology Unit has undertaken the Electron Microscopy part.

Oihane Lakar | EurekAlert!
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