Computational investigations of selected enzymes from two iron and α-ketoglutarate-dependent families

• Published in: Physical chemistry chemical physics : PCCP 2021-10, Vol.23 (39), p.22227-2224
• Main Authors: Berger, Madison B, Walker, Alice R, Vázquez-Montelongo, Erik Antonio, Cisneros, G. Andrés
• Format: Article
• Language: English
• Subjects: Alkylation; Dealkylation; Deoxyribonucleic acid; DNA; Electronic structure; Enzymes; Eukaryotes; Homology; Iron; Substrates
• ISSN: 1463-9076; 1463-9084
• DOI: 10.1039/d1cp03800a

DNA alkylation is used as the key epigenetic mark in eukaryotes, however, most alkylation in DNA can result in deleterious effects. Therefore, this process needs to be tightly regulated. The enzymes of the AlkB and Ten-Eleven Translocation (TET) families are members of the Fe and alpha-ketoglutarate-dependent superfamily of enzymes that are tasked with dealkylating DNA and RNA in cells. Members of these families span all species and are an integral part of transcriptional regulation. While both families catalyze oxidative dealkylation of various bases, each has specific preference for alkylated base type as well as distinct catalytic mechanisms. This perspective aims to provide an overview of computational work carried out to investigate several members of these enzyme families including AlkB, ALKB Homolog 2, ALKB Homolog 3 and Ten-Eleven Translocate 2. Insights into structural details, mutagenesis studies, reaction path analysis, electronic structure features in the active site, and substrate preferences are presented and discussed. AlkB and TET are two members of the Fe and α-ketoglutarate dependent superfamily of enzymes. This perspective provides an overview of computational investigations that have been carried out to study selected members of these two families.