Emergence of pyridoxal phosphorylation through a promiscuous ancestor during the evolution of hydroxymethyl pyrimidine kinases |
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Authors: | Victor Castro-Fernandez Felipe Bravo-Moraga Cesar A. Ramirez-Sarmiento Victoria Guixe |
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Affiliation: | Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago, Chile |
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Abstract: | In the family of ATP-dependent vitamin kinases, several bifunctional enzymes that phosphorylate hydroxymethyl pyrimidine (HMP) and pyridoxal (PL) have been described besides enzymes specific towards HMP. To determine how bifunctionality emerged, we reconstructed the sequence of three ancestors of HMP kinases, experimentally resurrected, and assayed the enzymatic activity of their last common ancestor. The latter has ∼8-fold higher specificity for HMP due to a glutamine residue (Gln44) that is a key determinant of the specificity towards HMP, although it is capable of phosphorylating both substrates. These results show how a specific enzyme with catalytic promiscuity gave rise to current bifunctional enzymes. |
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Keywords: | HMP, 4-amino-5-hydroxymethyl-2-methylpyrimidine HMPK, 4-amino-5-hydroxymethyl-2-methylpyrimidine kinase PL, pyridoxal PLK, pyridoxal kinase PLP, pyridoxal-5&prime -phosphate THZK, 4-methyl-5-β-hydroxy-ethylthiazole kinase |
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