Enzyme - Inorganic diphosphatase

Alternative Name(s)
  • Inorganic pyrophosphatase.
  • Diphosphate phosphohydrolase.
  • Pyrophosphate phosphohydrolase.

Catalytic Activity

diphosphate + H2O = H(+) + 2 phosphate


There are no Cofactors for this Enzyme

Reaction Mechanism

    Soluble inorganic pyrophosphate is present in all organisms, and is essential for cell growth. It provides an entropic pull for biosynthetic reactions involving nucleotide triphosphates by irreversibly hydrolysing the pyrophosphate product to orthophosphate. The phosphoryltransferase activity is an ancient one, and there are functional similarities between the active site of this enzyme and alkaline phosphatase and other divalent cation containing enzymes such as exonucleases and polymerases.

    This reaction begins with the coordination of three divalent metal ions into the active site as well as a water molecule from the aqueous solution. The metal ions coordinate a diphosphate into the active site while Asp89 deprotonates a water molecule. The resulting hydroxide attacks the proximal phosphate. This, in combination with the metals dissociating from the active site results in the release of two phosphate molecules. His21 and His86 are responsible for divalent metal selectivity and are major features distinguishing the Mtb PPiase from other characterised PPiases but aren't shown in this mechanism because they don't directly contribute to the catalysis reaction.
    Catalytic Residues
    AA Uniprot Uniprot Resid PDB PDB Resid
    Asp 57 4z71 66
    Asp 89 4z71 98
    Asp 52 4z71 61
    Glu 8 4z71 17
    Asp 84 4z71 93
    Tyr 42 4z71 51
    Step Components

    overall product formed, proton transfer, overall reactant used, coordination to a metal ion, bimolecular nucleophilic substitution

    Step 1.

    A divalent metal ion M3 binds to the PPiase, which already contains the divalent metal ion M1 in its active site. The presence of the two metal ions enable the binding of PPi together with a third divalent metal ion: M2.

    Step 2.

    The binding events are followed by the deprotonation of a water molecule by Asp89 and subsequent attack on the adjacent phosphate group of PPi by the resulting hydroxide, leading to the formation of the products.

    Step 3.

    After catalysis, ion M3 leaves the active site, followed by both phosphates and M2. Also, Asp89 is deprotonated (here inferred to be by a water molecule from solvent), thereby restoring the initial state of enzyme.


    The products of the reaction.

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Protein name Organism
Probable manganese-dependent inorganic pyrophosphatase Listeria welshimeri serovar 6b (strain ATCC 35897 / DSM 20650 / SLCC5334)
Inorganic pyrophosphatase, mitochondrial Baker's yeast
Putative pyrophosphatase PpaX Caldanaerobacter subterraneus subsp. tengcongensis (strain DSM 15242 / JCM 11007 / NBRC 100824 / MB4)
Soluble inorganic pyrophosphatase 1 Mouse-ear cress
Inorganic pyrophosphatase 2 Mouse-ear cress