08 February 2024

Scientists have investigated an enzyme that repairs DNA

Specialists from the Institute of Chemical Biology and Basic Medicine (ICBPM) of the Siberian Branch of the Russian Academy of Sciences have studied an enzyme that can remove damage from a DNA molecule and restore its structure. The results of the study have been published in the International Journal of Molecular Sciences.

The ALKBH3 enzyme has a complex mechanism of action, and it is not entirely clear how it interacts with the DNA molecule. The scientists identified which proteins in the enzyme structure interact in DNA and removed them to describe their role in the enzymatic process.

"Information about the contacts between the enzyme and the damaged DNA target is usually obtained by X-ray analysis of protein crystals. Such crystals are often impossible to obtain for structurally mobile enzymes containing weakly ordered domains, which ALKBH3 dioxygenase is. We have shown for the first time that the decrease in the reactivity of mutant (artificially altered) forms of dioxygenase is directly related to a decrease in the number of beta folds and an increase in the proportion of alpha-helices in the structure," says Lubov Kanazhevskaya, Ph.D., a researcher at the Center for Mass Spectrometric Analysis of IHBFM.

The obtained data can be used for the development of drugs aimed at inhibiting the undesirable activity of the enzyme ALKBH3 in cells of malignant tumors. Also, the results can be used in determining the activity of this enzyme in a living cell. This may give a prognosis about the development of certain pathologies associated with genomic DNA damage.

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