title: Reaction mechanism of deoxyribonucleotidase: a theoretical study.
abstract: 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.
authors.affiliation: Theoretical Chemistry, Department of Biotechnology, Royal Institute of Technology, ALBANOVA, SE-106 91 Stockholm, Sweden.
authors.forename: Fahmi
authors.initials: F
authors.lastname: Himo
authors.forename: Jing-Dong
authors.initials: JD
authors.lastname: Guo
authors.forename: Agnes
authors.initials: A
authors.lastname: Rinaldo-Matthis
authors.forename: Pär
authors.initials: P
authors.lastname: Nordlund
mesh_terms: 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
chemical_list: D010755:Organophosphates; C063766:5'(3')-nucleotidase; D015720:5'-Nucleotidase