Contribution of Nudt12 enzyme to differentially methylated dinucleotides of 5’RNA cap structure

Łukaszewicz, Maciej; Mrozek, A.; Bojarska, Elzbieta; Stelmach, Joanna; Stępiński, Janusz; Darżynkiewicz, Edward

doi:10.1016/j.bbagen.2023.130400

Cited by 1 publication

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“… 2018 ; Lukaszewicz et.al. 2023 ). The resolved structure of zfMTH1 contains three calcium ions in the Nudix-box motif (PDB 5TON) and comparison of the binding calcium to zfMTH1 with the binding magnesium ions to human Nudt15 (PDB 5BON) has shown that two positions of Ca 2+ and Mg 2+ overlap and the third calcium ion binds to a different position in relation to the remaining two magnesium ions of Nudt15 (Jemth et.al.…”

Section: Resultsmentioning

confidence: 99%

Mammalian Nudt15 hydrolytic and binding activity on methylated guanosine mononucleotides

Lukaszewicz,

Ferenc-Mrozek,

Kokosza

et al. 2023

Eur Biophys J

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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 m7GDP, 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 m7GDP, its triphosphate form m7GTP, and the trimethylated counterparts (m32,2,7GDP and m32,2,7GTP). Kinetic data revealed a moderate activity of Nudt15 toward these methylated mononucleotides compared to the dGTP substrate. However m7GDP and m32,2,7GDP 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.

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Section: Resultsmentioning

confidence: 99%