10.1021/jp1109256.s001 Saumya Tiwari Saumya Tiwari Neha Agnihotri Neha Agnihotri P.C. Mishra P.C. Mishra Quantum Theoretical Study of Cleavage of the Glycosidic Bond of 2′-Deoxyadenosine: Base Excision-Repair Mechanism of DNA by MutY American Chemical Society 2011 BHandHLYP MutYThe enzyme adenine DNA glycosylase acid water molecules B 3LYP level integral equation formalism reaction mechanism gas phase MP calculation polarizable continuum model complex catalyze base excision repair 2011-03-31 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Quantum_Theoretical_Study_of_Cleavage_of_the_Glycosidic_Bond_of_2_Deoxyadenosine_Base_Excision_Repair_Mechanism_of_DNA_by_MutY/2674957 The enzyme adenine DNA glycosylase, also called MutY, is known to catalyze base excision repair by removal of adenine from the abnormal 2′-deoxyadenosine:8-oxo-2′-deoxyguanosine pair in DNA. The active site of the enzyme was considered to consist of a glutamic acid residue along with two water molecules. The relevant reaction mechanism involving different barrier energies was studied theoretically. Molecular geometries of the various molecules and complexes involved in the reaction, e.g., the reactant, intermediate, and product complexes as well as transition states, were optimized employing density functional theory at the B3LYP/6-31G(d,p) level in the gas phase. It was followed by single-point energy calculations at the B3LYP/AUG-cc-pVDZ, BHandHLYP/AUG-cc-pVDZ, and MP2/AUG-cc-pVDZ levels in the gas phase. Single-point energy calculations were also carried out at the B3LYP/AUG-cc-pVDZ and BHandHLYP/AUG-cc-pVDZ levels in aqueous media as well as in the solvents chlorobenzene and dichloroethane. For the solvation calculations, the integral equation formalism of the polarizable continuum model (IEF-PCM) was employed. It is found that glutamic acid along with two water molecules would effectively cleave the glycosidic bond of adenosine by a new two-step reaction mechanism proposed here which is different from the three-step mechanism proposed by other authors earlier regarding the working mechanism of MutY.