PNNL

Abstract

Letter to the Editor. Biological context Deinococcus radiodurans is a bacterium that is extremely resistant to the lethal and mutagenic effects of ionizing radiation, ultraviolet radiation, and other physical and chemical DNA-damaging agents (Battista, 1997). It has been suggested that this resistance is due to unusually efficient DNA repair mechanisms (Minton, 1994). Analysis of the complete genome sequence of D. radiodurans reveals a full suite of genes with potential DNA repair activities (White et al, 1999), essentially all of which have functional homologues in other procaryotes. These hypothetical DNA repair genes display a high amount of redundancy and include 21 genes that have sequence homology with the Nudix family of polyphosphate pyrophosphohydrolases (Bessman et al., 1996). Nudix proteins are identified by the consensus sequence GX5EX7REUXEEXGU (where U = I, L, or V and X = any amino acid) that forms part of the catalytic site for diphosphate hydrolysis (Bessman et al., 1996). Consequently, a nucleoside diphosphate linkage is a feature common in Nudix substrates that include NADH, nucleotide sugars, dinucleotide polyphosphates, and (deoxy)ribonucleoside triphosphates (NTPs). The general biochemical function of the Nudix family of proteins is believed to be sanitizing the cell (Bessman et al., 1996). For example, MutT preferably hydrolyzes the promutagenic NTP 7,8-dihydro-8-oxoguanosine triphosphate to nucleotide monophosphate and inorganic phosphate. Despite the identification of over 450 putative Nudix proteins in genomes on the basis of the Nudix consensus sequence (Gabelli et al., 2001), few Nudix protein structures have been determined (Holbrook et al., 2002). To better understand the relevance, function, and mechanism of the Nudix family of proteins, and to better understand the roles played by the hypothetical D. radiodurans Nudix proteins in radiation-resistance, we have crystallized the hypothetical D.