Insights into the Direct Oxidative Repair of Etheno Lesions: MD and QM/MM Study on the Substrate Scope of ALKBH2 and AlkB.

ABSTRACT: E. coli AlkB and human ALKBH2 belong to the AlkB family enzymes, which contain several α-ketoglutarate (α-KG)/Fe(II)-dependent dioxygenases that repair alkylated DNA. Specifically, the AlkB enzymes catalyze decarboxylation of α-KG to generate a high-valent Fe(IV)-oxo species that oxidizes alkyl groups on DNA adducts. AlkB and ALKBH2 have been reported to differentially repair select etheno adducts, with preferences for 1,N⁶-ethenoadenine (1,N⁶-εA) and 3,N⁴-ethenocytosine (3,N⁴-εC) over 1,N²-ethenoguanine (1,N²-εG). However, N²,3-ethenoguanine (N²,3-εG), the most common etheno adduct, is not repaired by the AlkB enzymes. Unfortunately, a structural understanding of the differential activity of E. coli Al

SUBMITTER: Lenz SAP 

PROVIDER: S-EPMC7669730 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature