Structure of a Nudix protein from Pyrobaculum aerophilum reveals a dimer with two intersubunit β-­sheets

Nudix proteins, formerly called MutT homolog proteins, are a large family of proteins that play an important role in reducing the accumulation of potentially toxic compounds inside the cell. They hydrolyze a wide variety of substrates that are mainly composed of a nucleoside diphosphate linked to some other moiety X and thus are called Nudix hydrolases. Here, the crystal structure of a Nudix hydrolase from the hyperthermophilic archaeon Pyrobaculum aerophilum is reported. The structure was determined by the single-wavelength anomalous scattering method with data collected at the peak anomalous wavelength of an iridium-derivatized crystal. It reveals an extensive dimer interface, with each subunit contributing two strands to the β-sheet of the other subunit. Individual subunits consist of a mixed highly twisted and curved β-sheet of 11 β-strands and two α-helices, forming an α–β–α sandwich. The conserved Nudix box signature motif, which contains the essential catalytic residues, is located at the first α-helix and the β-strand and loop preceding it. The unusually short connections between secondary-structural elements, together with the dimer form of the structure, are likely to contribute to the thermostability of the P. aerophilum Nudix protein.