L-Valine L-Phenylalanine L-Arginine

The study, entitled "Moonlighting Proteins HAL3 and VHS3 Form a Heteromeric PPCDC with YKL088w in Yeast CoA Biosynthesis" and published in Nature Chemical Biology, L-Histidine/L-HISTIDINE_71-00-1.html">L-HISTIDINE was carried out by researchers of the UAB Department of Biochemistry and Molecular Biology and the University of Stellenbosch, South Africa, under the coordination of Dr Joaquin Ariño.

PPCDC is an essential enzyme and plays a key role in the synthesis of Coenzyme A, L-Methionine/L-METHIONINE_63-68-3.html">L-METHIONINE a molecule universally conserved in eukaryotic cells which intervenes in the degradation of fatty acids, carbohydrates and amino acids in all organisms (bacteria, L-Arginine/L-ARGININE_74-79-3.html">L-ARGININE plants and humans). The gene involved in the formation of PPCDC was identified in plants and humans. In both cases, the enzyme is a homotrimeric complex, i.e. it is formed by the association of three identical proteins. The interaction of the three is precisely what determines the formation of the three identical active sites- areas of the enzyme in which the catalytic process takes place - it contains. However, its nature in the yeast Saccharomyces cerevisiae was a mystery to researchers, given that this organism seems to contain three genes potentially capable of coding a PPCDC (HAL3, VHS3 and YKL088w), but none of them could be associated with this function.

The research carried out by the UAB group has helped to clarify this apparent paradox by demonstrating that the S. cerevisiae enzyme exists as a heterotrimer, i.e. it is formed by 3 non-identical proteins. One of these proteins is necessarily coded by the YKL088w gene (which explains its essential nature) and the other can be two molecules coded by either HAL3 or VHS3, or even one of each. The active site in this case is made up of amino acids of two different proteins: the one coded by gene YKL088w, which provides a catalytic cysteine, and the one coded by HAL3 or VHS3, which provides a histidine, also essential for the catalysis.