6fl4
A. thaliana NUDT1 in complex with 8-oxo-dGTP
Structural highlights
FunctionNUDT1_ARATH Mediates the hydrolysis of some nucleoside diphosphate derivatives. Its substrate specificity is unclear. In vitro, it can use NTP, dNTP, 8-oxo-GTP, 8-oxo-dGTP, dGTP, dATP, dTTP or dihydroneopterin triphosphate (DHNTP) as substrate. Has some NADH pyrophosphatase activity in vitro; however, such activity may not be relevant in vivo due to the high concentration of manganese used during the experiments. Plays an important role in protection against oxidative DNA and RNA damage by removing oxidatively damaged form of guanine.[1] [2] [3] Publication Abstract from PubMedArabidopsis thaliana NUDT1 (AtNUDT1) belongs to the Nudix family of proteins, which have a diverse range of substrates, including oxidized nucleotides such as 8-oxo-dGTP. The hydrolysis of oxidized dNTPs is highly important as it prevents their incorporation into DNA, thus preventing mutations and DNA damage. AtNUDT1 is the sole Nudix enzyme from A. thaliana shown to have activity against 8-oxo-dGTP. We present the structure of AtNUDT1 in complex with 8-oxo-dGTP. Structural comparison with bacterial and human homologues reveals a conserved overall fold. Analysis of the 8-oxo-dGTP binding mode shows that the residues Asn76 and Ser89 interact with the O8 atom of the substrate, a feature not observed in structures of protein homologues solved to date. Kinetic analysis of wild-type and mutant AtNUDT1 confirmed that these active site residues influence 8-oxo-dGTP hydrolysis. A recent study showed that AtNUDT1 is also able to hydrolyze terpene compounds. The diversity of reactions catalyzed by AtNUDT1 suggests that this Nudix enzyme from higher plants has evolved in a manner distinct to those from other organisms. Crystal Structure and Substrate Specificity of the 8-oxo-dGTP Hydrolase NUDT1 from Arabidopsis thaliana.,Jemth AS, Scaletti E, Carter M, Helleday T, Stenmark P Biochemistry. 2019 Feb 19;58(7):887-899. doi: 10.1021/acs.biochem.8b00950. Epub, 2019 Jan 16. PMID:30614695[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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