Reaction mechanism of deoxyribonucleotidase: a theoretical study.
The reaction mechanism of human deoxyribonucleotidase (dN) is studied using high-level quantum-chemical methods. dN catalyzes the dephosphorylation of deoxyribonucleoside monophosphates (dNMPs) to their nucleoside form in human cells. Large quantum models are employed (99 atoms) based on a recent X-ray crystal structure. The calculations support the proposed mechanism in which Asp41 performs a nucleophilic attack on the phosphate to form a phospho-enzyme intermediate. Asp43 acts in the first step as an acid, protonating the leaving nucleoside, and in the second step as a base, deprotonating the lytic water. No pentacoordinated intermediates could be located.
Himo
Fahmi
F
Theoretical Chemistry, Department of Biotechnology, Royal Institute of Technology, ALBANOVA, SE-106 91 Stockholm, Sweden.
Guo
Jing-Dong
JD
Rinaldo-Matthis
Agnes
A
Nordlund
Pär
P
D015720:5'-Nucleotidase / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006868:Hydrolysis; D008956:Models, Chemical; D008958:Models, Molecular; D015233:Models, Statistical; D010755:Organophosphates / Q000737:chemistry; D010766:Phosphorylation; D011789:Quantum Theory
D010755:Organophosphates; C063766:5'(3')-nucleotidase; D015720:5'-Nucleotidase