Mammalian Nudt15 Hydrolytic and Binding Activity on Methylated Guanosine Mononucleotides

Overview

Journal Eur Biophys J

Specialty Biophysics

Date 2023 Aug 29

PMID 37644211

Authors

Maciej Lukaszewicz

Aleksandra Ferenc-Mrozek

Julia Kokosza

Anna Stefaniuk

Janusz Stepinski

Elzbieta Bojarska

Edward Darzynkiewicz

Affiliations

Soon will be listed here.

Abstract

The Nudt15 enzyme of the NUDIX protein family is the subject of extensive study due to its action on thiopurine drugs used in the treatment of cancer and inflammatory diseases. In addition to thiopurines, Nudt15 is enzymatically active in vitro on several nucleotide substrates. It has also been suggested that this enzyme may play a role in 5'RNA turnover by hydrolyzing mGDP, a product of mRNA decapping. However, no detailed studies on this substrate with Nudt15 are available. Here, we analyzed the enzymatic activity of Nudt15 with mGDP, its triphosphate form mGTP, and the trimethylated counterparts (mGDP and mGTP). Kinetic data revealed a moderate activity of Nudt15 toward these methylated mononucleotides compared to the dGTP substrate. However mGDP and mGDP showed a distinct stabilization of Nudt15 upon ligand binding, in the same range as dGTP, and thus these two mononucleotides may be used as leading structures in the design of small molecule binders of Nudt15.

Citing Articles

Special Issue: 18th Congress of the Polish Biophysical Society.

Antosiewicz J, Gilbert R, Marszalek P Eur Biophys J. 2023; 52(6-7):483-486.

PMID: 37882816 DOI: 10.1007/s00249-023-01688-3.

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