Opis

• Tytuł:
  Insight into the Binding and Hydrolytic Preferences of hNudt16 Based on Nucleotide Diphosphate Substrates
• Twórca:
  Chrabąszczewska, Magdalena;
  Winiewska-Szajewska, Maria;
  Ostrowska, Natalia;
  Bojarska, Elżbieta;
  Stępiński, Janusz;
  Mancewicz, Łukasz;
  Łukaszewicz, Maciej;
  Trylska, Joanna;
  Taube, Michał;
  Kozak, Maciej;
  Darżynkiewicz, Edward;
  Grzela, Renata
• Opis:
  Nudt16 is a member of the NUDIX family of hydrolases that show specificity towards substrates consisting of a ucleoside diphosphate linked to another moiety X. Several substrates for hNudt16 and various possible biological functions have been reported. However, some of these reports contradict each other and studies comparing the substrate specificity of the hNudt16 protein are limited. Therefore, we quantitatively compared the affinity of hNudt16 towards a set of previously published substrates, as well as identified novel potential substrates. Here, we show that hNudt16 has the highest affinity towards IDP and GppG, with Kd below 100 nM. Other tested ligands exhibited a weaker affinity of several orders of magnitude. Among the investigated compounds, only IDP, GppG, m7GppG, AppA, dpCoA, and NADH were hydrolyzed by hNudt16 with a strong substrate preference for inosine or guanosine containing compounds. A new identified substrate for hNudt16, GppG, which binds the enzyme with an affinity comparable to that of IDP, suggests another potential regulatory role of this protein. Molecular docking of hNudt16-ligand binding inside the hNudt16 pocket revealed two binding modes for representative substrates. Nucleobase stabilization by Π stacking interactions with His24 has been associated with strong binding of hNudt16 substrates.
• Dostępność obiektu:
  Dostęp otwarty
• Data:
  2021
• Typ:
  Article;
  PeerReviewed
• Język:
  angielski
• Format:
  application/pdf
• Relacja: http://eprints.ibb.waw.pl/2095 ;http://doi.org/10.3390/ijms222010929 ;doi:10.3390/ijms222010929
• Temat i słowa kluczowe:
  Q Science (General)
• Identyfikator: http://eprints.ibb.waw.pl/2095/1/ijms-22-10929.pdf ;
  Chrabąszczewska, Magdalena and Winiewska-Szajewska, Maria and Ostrowska, Natalia and Bojarska, Elżbieta and Stępiński, Janusz and Mancewicz, Łukasz and Łukaszewicz, Maciej and Trylska, Joanna and Taube, Michał and Kozak, Maciej and Darżynkiewicz, Edward and Grzela, Renata (2021) Insight into the Binding and Hydrolytic Preferences of hNudt16 Based on Nucleotide Diphosphate Substrates. International Journal of Molecular Sciences, 22 (20). p. 10929. ISSN 1422-0067
• Dostawca danych:
  Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk
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