Comparative Analysis of Exo-and Endonuclease Activities of APE1-like Enzymes

Anastasiia T. Davletgildeeva, Alexandra A. Kuznetsova, Darya S. Novopashina, Alexander A. Ishchenko, Murat Saparbaev, Olga S. Fedorova, Nikita A. Kuznetsov

Результат исследования: Научные публикации в периодических изданияхстатьярецензирование

Аннотация

Apurinic/apyrimidinic (AP)-endonucleases are multifunctional enzymes that are required for cell viability. AP-endonucleases incise DNA 5′ to an AP-site; can recognize and process some damaged nucleosides; and possess 3′-phosphodiesterase, 3′-phosphatase, and endoribonu-clease activities. To elucidate the mechanism of substrate cleavage in detail, we analyzed the effect of mono-and divalent metal ions on the exo-and endonuclease activities of four homologous APE1-like endonucleases (from an insect (Rrp1), amphibian (xAPE1), fish (zAPE1), and from hu-mans (hAPE1)). It was found that the enzymes had similar patterns of dependence on metal ions’ concentrations in terms of AP-endonuclease activity, suggesting that the main biological function (AP-site cleavage) was highly conserved among evolutionarily distant species. The efficiency of the 3′-5′ exonuclease activity was the highest in hAPE1 among these enzymes. In contrast, the en-doribonuclease activity of the enzymes could be ranked as hAPE1 ≈ zAPE1 ≤ xAPE1 ≤ Rrp1. Taken together, the results revealed that the tested enzymes differed significantly in their capacity for substrate cleavage, even though the most important catalytic and substrate-binding amino acid residues were conserved. It can be concluded that substrate specificity and cleavage efficiency were controlled by factors external to the catalytic site, e.g., the N-terminal domain of these enzymes.

Язык оригиналаанглийский
Номер статьи2869
ЖурналInternational Journal of Molecular Sciences
Том23
Номер выпуска5
DOI
СостояниеОпубликовано - 1 мар. 2022

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  • 1.04 ХИМИЧЕСКИЕ НАУКИ
  • 2.04 ХИМИЧЕСКИЕ ТЕХНОЛОГИИ
  • 1.06 БИОЛОГИЧЕСКИЕ НАУКИ

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