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

This review concerns enzymes that can degrade nucleoside 5'-tetra- and pent aphosphates (p(4)N and p(5)N) and those that can degrade various dinucleosi de polyphosphates (Np3-6N'). Most of these enzymes are hydrolases, and they occur in all types of organisms. Certain fungi and protozoa also possess s pecific NpnN' phosphorylases. Specific p(4)N hydrolases have been demonstra ted in mammals and in plants. In yeast, p(4)N and p(5)N are hydrolyzed by e xopolyphosphatases. Among other hydrolases that can degrade these minor mon onucleotides are phosphatases, apyrase, and (asymmetrical) Np4N' hydrolase, as well as the nonspecific adenylate deaminase. NpnN's are good substrates for Type I phosphodiesterases and nucleotide pyrophosphatases, and diadeno sine polyphosphates are easily deaminated to diinosine polyphosphates by no nspecific adenylate deaminases. Specific Np3N' hydrolases occur in both pro karyotes and eukaryotes. Interestingly, the human fragile histidine triad ( Fhit) tumor suppressor protein appears to be a typical Np3N' hydrolase. Amo ng the specific Np4N' hydrolases are asymmetrically cleaving ones, which ar e 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 sim ilar to that of the human Fhit/Np3N' hydrolase. Very recently, a typical (a symmetrical) Np4N' hydrolase has been demonstrated for the first time in a bacterium-the pathogenic Bartonella bacilliformis. Another novelty is the d iscovery of diadenosine 5',5"'-P-1,P-6-hexaphosphate hydrolases in budding and fission yeasts and in mammalian cells, These enzymes and the (asymmetri cal) Np4N' hydrolases have the amino acid motif typical of the MutT (or Nud ix hydrolase) family. In contrast, the Schizosaccharomyces pombe Ap(4)A/Ap( 3)A hydrolase, the human Fhit protein, and the yeast NpnN' phosphorylases b elong to a superfamily GAFH, which includes the histidine triad proteins. ( C) 2000 Elsevier Science Inc. All rights reserved.