6FL4

A. thaliana NUDT1 in complex with 8-oxo-dGTP

Summary for 6FL4

• Entry DOI: 10.2210/pdb6fl4/pdb
• Descriptor: Nudix hydrolase 1, MAGNESIUM ION, 8-OXO-2'-DEOXYGUANOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: 8-oxo-dgtp, hydrolase
• Biological source: Arabidopsis thaliana (Mouse-ear cress)
• Total number of polymer chains: 2
• Total formula weight: 33890.69

Authors

Jemth, A.S.,Scaletti-Hutchinson, E.,Carter, M.,Helleday, T.,Stenmark, P. (deposition date: 2018-01-25, release date: 2019-02-06, Last modification date: 2024-05-08)

Primary citation

Jemth, A.S.,Scaletti, E.,Carter, M.,Helleday, T.,Stenmark, P.
Crystal Structure and Substrate Specificity of the 8-oxo-dGTP Hydrolase NUDT1 from Arabidopsis thaliana.
Biochemistry, 58:887-899, 2019

PubMed Abstract: Arabidopsis 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.

PubMed: 30614695
DOI: 10.1021/acs.biochem.8b00950

Experimental method

X-RAY DIFFRACTION (1.6 Å)