Crystal structure of RS21-C6, involved in nucleoside triphosphate pyrophosphohydrolysis.
RS21-C6, which is highly expressed in all vertebrate genomes and green plants, is proposed to have nucleoside triphosphate pyrophosphohydrolase activity. Here, we report the crystal structures of the core fragment of RS21-C6, named RSCUT, and the complex with the substrate 5-methyl dCTP. The refined structure of RSCUT consists mainly of alpha-helices and shows formation of a tightly associated tetramer. On the basis of the structure of the RSCUT-m5dCTP complex and the results of pyrophosphatase activity assays, several key residues involved in the substrate binding of RS21-C6 have been identified. Tetramer formation is shown to be required for substrate binding.
Wu
Beili
B
Tsinghua-IBP-Nankai Joint Research Group for Structural Biology, Tsinghua University, Beijing 100084, China.
Liu
Yuanfeng
Y
Zhao
Qiang
Q
Liao
Shuang
S
Zhang
Jun
J
Bartlam
Mark
M
Chen
Weifeng
W
Rao
Zihe
Z
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006868:Hydrolysis; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000235:genetics; D011755:Pyrophosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D011755:Pyrophosphatases; C519682:RS21-C6 protein, mouse; C020020:dUTP pyrophosphatase; C021895:nucleoside triphosphate pyrophosphatase