posted on 2019-01-07, 00:00authored byAnn-Sofie Jemth, Emma Scaletti, Megan Carter, Thomas Helleday, Pål Stenmark
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.