Specific and nonspecific enzymes involved in the catabolism of mononucleoside and dinucleoside polyphosphates

Abstract

This review concerns enzymes that can degrade nucleoside 5′-tetra- and pentaphosphates (p 4N and p 5N) and those that can degrade various dinucleoside polyphosphates (Np 3–6N′). Most of these enzymes are hydrolases, and they occur in all types of organisms. Certain fungi and protozoa also possess specific Np n N′ phosphorylases. Specific p 4N hydrolases have been demonstrated in mammals and in plants. In yeast, p 4N and p 5N are hydrolyzed by exopolyphosphatases. Among other hydrolases that can degrade these minor mononucleotides are phosphatases, apyrase, and (asymmetrical) Np 4N′ hydrolase, as well as the nonspecific adenylate deaminase. Np n N′s are good substrates for Type I phosphodiesterases and nucleotide pyrophosphatases, and diadenosine polyphosphates are easily deaminated to diinosine polyphosphates by nonspecific adenylate deaminases. Specific Np 3N′ hydrolases occur in both prokaryotes and eukaryotes. Interestingly, the human fragile histidine triad (Fhit) tumor suppressor protein appears to be a typical Np 3N′ hydrolase. Among the specific Np 4N′ hydrolases are asymmetrically cleaving ones, which are typical of higher eukaryotes, and symmetrically cleaving enzymes found in Physarum polycephalum and in many bacteria. An enzyme that hydrolyzes both diadenosine tetraphosphate and diadenosine triphosphate has been found in the fission yeast Schizosaccharomyces pombe. Its amino acid sequence is similar to that of the human Fhit/Np 3N′ hydrolase. Very recently, a typical (asymmetrical) Np 4N′ hydrolase has been demonstrated for the first time in a bacterium—the pathogenic Bartonella bacilliformis. Another novelty is the discovery of diadenosine 5′,5′′′- P 1, P 6-hexaphosphate hydrolases in budding and fission yeasts and in mammalian cells. These enzymes and the (asymmetrical) Np 4N′ hydrolases have the amino acid motif typical of the MutT (or Nudix hydrolase) family. In contrast, the Schizosaccharomyces pombe Ap 4A/Ap 3A hydrolase, the human Fhit protein, and the yeast Np n N′ phosphorylases belong to a superfamily GAFH, which includes the histidine triad proteins.