TY - JOUR

T1 - Dealkylation of Macromolecules by Eukaryotic α-Ketoglutarate-Dependent Dioxygenases from the AlkB-like Family

AU - Davletgildeeva, Anastasiia T.

AU - Kuznetsov, Nikita A.

PY - 2024/9

Y1 - 2024/9

N2 - Alkylating modifications induced by either exogenous chemical agents or endogenous metabolites are some of the main types of damage to DNA, RNA, and proteins in the cell. Although research in recent decades has been almost entirely devoted to the repair of alkyl and in particular methyl DNA damage, more and more data lately suggest that the methylation of RNA bases plays an equally important role in normal functioning and in the development of diseases. Among the most prominent participants in the repair of methylation-induced DNA and RNA damage are human homologs of Escherichia coli AlkB, nonheme Fe(II)/α-ketoglutarate-dependent dioxygenases ABH1–8, and FTO. Moreover, some of these enzymes have been found to act on several protein targets. In this review, we present up-to-date data on specific features of protein structure, substrate specificity, known roles in the organism, and consequences of disfunction of each of the nine human homologs of AlkB. Special attention is given to reports about the effects of natural single-nucleotide polymorphisms on the activity of these enzymes and to potential consequences for carriers of such natural variants. © 2024 by the authors.

AB - Alkylating modifications induced by either exogenous chemical agents or endogenous metabolites are some of the main types of damage to DNA, RNA, and proteins in the cell. Although research in recent decades has been almost entirely devoted to the repair of alkyl and in particular methyl DNA damage, more and more data lately suggest that the methylation of RNA bases plays an equally important role in normal functioning and in the development of diseases. Among the most prominent participants in the repair of methylation-induced DNA and RNA damage are human homologs of Escherichia coli AlkB, nonheme Fe(II)/α-ketoglutarate-dependent dioxygenases ABH1–8, and FTO. Moreover, some of these enzymes have been found to act on several protein targets. In this review, we present up-to-date data on specific features of protein structure, substrate specificity, known roles in the organism, and consequences of disfunction of each of the nine human homologs of AlkB. Special attention is given to reports about the effects of natural single-nucleotide polymorphisms on the activity of these enzymes and to potential consequences for carriers of such natural variants. © 2024 by the authors.

KW - catalytic mechanism

KW - dealkylation

KW - dioxygenase

KW - enzyme disfunction

KW - macromolecule alkylation

KW - single-nucleotide polymorphism

UR - https://www.mendeley.com/catalogue/d985497a-60b3-3154-9d41-da4afc01a6a4/

U2 - 10.3390/cimb46090622

DO - 10.3390/cimb46090622

M3 - Article

C2 - 39329974

VL - 46

SP - 10462

EP - 10491

JO - Current issues in molecular biology

JF - Current issues in molecular biology

SN - 1467-3037

IS - 9

ER -