Emergence of pyridoxal phosphorylation through a promiscuous ancestor during the evolution of hydroxymethyl pyrimidine kinases

Castro-Fernandez, Victor; Bravo-Moraga, Felipe; Ramirez-Sarmiento, Cesar A; Guixe, Victoria

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 similar to 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. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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Título según WOS: Emergence of pyridoxal phosphorylation through a promiscuous ancestor during the evolution of hydroxymethyl pyrimidine kinases
Título según SCOPUS: Emergence of pyridoxal phosphorylation through a promiscuous ancestor during the evolution of hydroxymethyl pyrimidine kinases
Título de la Revista: FEBS LETTERS
Volumen: 588
Número: 17
Editorial: Wiley
Fecha de publicación: 2014
Página de inicio: 3068
Página final: 3073
Idioma: English
URL: http://linkinghub.elsevier.com/retrieve/pii/S0014579314004955
DOI:

10.1016/j.febslet.2014.06.033

Notas: ISI, SCOPUS - ISI