Premium
Computational study of the phosphoryl donor activity of dihydroxyacetone kinase from ATP to inorganic polyphosphate
Author(s) -
Bordes Isabel,
GarcíaJunceda Eduardo,
SánchezMoreno Israel,
Castillo Raquel,
Moliner Vicent
Publication year - 2018
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.25520
Subject(s) - dihydroxyacetone , dihydroxyacetone phosphate , chemistry , polyphosphate , enzyme , dhap , adenosine triphosphate , mutant , active site , kinase , stereochemistry , reaction mechanism , combinatorial chemistry , biochemistry , catalysis , phosphate , glycerol , gene
Adenosine triphosphate (ATP) is the main biological phosphoryl donor required in many enzymes including dihydroxyacetone kinases (DHAKs) that convert dihydroxyacetone (Dha) into dihydroxyacetone phosphate (Dha‐P), a key species with potential applications in synthesis. Herein, we present a theoretical study of the molecular mechanism for the phosphoryl transfer reaction from an inorganic polyphosphate to Dha catalyzed by DHAK from C. freundii . This is part of a project devoted to modify the phosphoryl donor specificity of this enzyme avoiding the use of the problematic direct addition of ATP. Based on the use of hybrid QM/MM potentials, with the QM region described by semiempirical and DFT methods, the reaction mechanism of the wild‐type enzyme and the most active experimentally measured mutant (Glu526Lys) with poly‐P as phosphoryl donor has been explored to elucidate the origin of the activity of this mutant. The similar energy barriers obtained in both systems confirm our previous studies on the binding step (Sánchez‐Moreno et al., Int. J. Mol. Sci . 2015 , 16 , 27835) suggesting that this mutation favors a more adequate position of the poly‐P in the active site for the following step, the chemical reaction, to take place.