화학공학소재연구정보센터
Chemical Physics Letters, Vol.631, 16-20, 2015
A QM/MM study of the 5'-AMP DNA hydrolysis of aprataxin
Aprataxin is a DNA repair enzyme that hydrolyzes the abnormal 5'-AMP termini of broken DNAs. Based on quantum mechanical/molecular mechanical (QM/MM) calculations, we found that the catalytic reaction proceeds in three steps; substrate protonation, DNA deadenylation and histidine-AMP intermediate hydrolysis. The calculated activation energies for the second and third reactions are 19.0 and 10.5 kcal mol(-1), which can be attributed to a penta-coordinated AMP-phosphoryl formation and closing of a water molecule, respectively. We also found that a histidine-AMP intermediate is hydrolyzed easily in the third step when a water molecule closes within 3 angstrom to the phosphorus nucleus. (C) 2015 Elsevier B.V. All rights reserved.