Conformational and Mechanistic Studies of AlkB and AlkBH2 DNA Demethylases

Document Type

Article

Publication Date

4-1-2019

Department

Department of Chemistry

Abstract

DNA demethylases play a crucial role in DNA repair mechanisms and have been linked to pathologies. AlkB enzyme and its human homolog AlkBH2 have been very intensively studied both experimentally and computationally. It is well known also that AlkB exhibits broader substrate specificity than AlkBH2. Applying MD and QM/MM methods here we focus on: i) on the differences between the dynamical properties and collective motions between both enzymes: ii) the different impact on the protein environment on the reaction mechanisms in AlkB and AlkBH2. The provided atomistic insight can be used in designing enzyme-selective inhibitors and demonstrate the power of computational methods to complement experimental studies.

Publication Title

The FASEB Journal Biochemistry and Molecular Biology

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