question: By which mechanism MutT proteins act against DNA lesions in bacteria?
answer: MutT proteins belong to a class of Nudix hydrolases. The common substrate structure for the proteins of the functionally diverse Nudix superfamily is nucleotide-diphosphate-X, where X is a large variety of leaving groups. The activities of Nudix hydrolases usually result in the release of an inorganic phosphate ion or of a product bearing a terminal phosphate moiety. MutT proteins hydrolyze 8-oxo-G nucleoside triphosphates/diphosphates to the corresponding nucleoside monophosphates and sanitize the nucleotide pool. MutT proteins cleave 8-oxo-dGTP (8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate) at the α-β position; they also cleave 8-oxo-dGTP at the β-γ phosphate bond at a rate of 3% of that recorded for hydrolysis at the α-β position. 8-oxo-dGTP induces A to C transversions when misincorporated in DNA opposite to template A. By hydrolyzing 8-oxo-dGTP before their incorporation into DNA, MutT proteins play a critical role in allowing bacteria to avoid A-to-C mutations, which are a hallmark of MutT deficiency. Thus, MutT proteins prevent oxidative DNA lesions, as part of the GO system. Oxidized nucleotides can occur when bacteria are exposed to reactive oxygen species. Also, reactive oxygen species are produced as side products of oxygen utilization, leading to the oxidation of nucleic acids and their precursor nucleotides. Distinct from the Escherichia coli MutT, which hydrolyzes 8-oxo-dGTP and 8-oxo-GTP, the mycobacterial proteins hydrolyze not only 8-oxo-dGTP and 8-oxo-GTP but also dCTP and 5-methyl-dCTP. Moreover, the hydrolysis of 8-oxo-dGTP and 8-oxo-GTP in mycobacteria seems to be catalysed in a two-stage mechanism, since MutT converts these oxidized nucleoside triphosphates to their corresponding nucleoside diphosphates, and not to monophosphates.