The MutT proteins or "Nudix" hydrolases, a family of versatile, widely distributed, "housecleaning" enzymes

Abstract

Our studies on the biochemical basis of spontaneous mutations took an interesting and unexpected turn when we discovered that a small region of amino acid homology between the MutT protein of Escherichia coli and the MutX protein of Streptococcus pneumoniae was involved in their nucleoside triphosphatase as well as their antimutator activities (1–3). Computer searches of the data banks revealed that this same small conserved region was present in a number of other proteins in organisms ranging from viruses to humans (2, 4). Most of these proteins containing the signature are coded for by open reading frames (orfs)1 whose products are either unidentified or of unknown function. We have been attempting, systematically, to identify and characterize enzymatic activities associated with these proteins, and it is now evident that nature has adopted this motif, originally identified as the active site of the nucleoside-triphosphate pyrophosphohydrolase of MutT (5, 6), and adapted it for use in many diverse reactions distinct from its function in the MutT protein. This short review summarizes our present knowledge of those reactions catalyzed by proteins harboring the MutT signature sequence and calls attention to a unique and versatile nucleotide binding and catalytic site. Although it might appear that the enzymes of this family act upon a wide variety of unrelated substrates, those characterized so far all hydrolyze a nucleoside diphosphate linked to some other moiety, X. For convenience, and to correct a misapprehension, we propose the mnemonic “nudix” hydrolase for this family of enzymes to replace the “MutT family.” Currently, this signature sequence is designated the “MutT pattern” in version 13.0 of the PROSITE data base of amino acid sequence motifs (7). This initial classification is misleading, because many, if not most, of these proteins are not involved directly in preventing mutations nor do they catalyze the archetypal nucleoside triphosphate pyrophosphohydrolysis reaction originally described for MutT itself (5, 6).