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Inorganic pyrophosphatases of Family II —two decades after their discovery
Author(s) -
Baykov Alexander A.,
Anashkin Viktor A.,
Salminen Anu,
Lahti Reijo
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12877
Subject(s) - pyrophosphatases , chemistry , allosteric regulation , metaphosphate , biochemistry , stereochemistry , enzyme , phosphate
Inorganic pyrophosphatases ( PP ases) convert pyrophosphate (PP i ) to phosphate and are present in all cell types. Soluble PP ases belong to three nonhomologous families, of which Family II is found in approximately a quarter of prokaryotic organisms, often pathogenic ones. Each subunit of dimeric canonical Family II PP ases is formed by two domains connected by a flexible linker, with the active site located between the domains. These enzymes require both magnesium and a transition metal ion (manganese or cobalt) for maximal activity and are the most active ( k cat ≈ 10 4 s −1 ) among all PP ase types. Catalysis by Family II PP ases requires four metal ions per substrate molecule, three of which form a unique trimetal center that coordinates the nucleophilic water and converts it to a reactive hydroxide ion. A quarter of Family II PP ases contain an autoinhibitory regulatory insert formed by two cystathionine β‐synthase ( CBS ) domains and one DRTGG domain. Adenine nucleotide binding either activates or inhibits the CBS domain‐containing PP ases, thereby tuning their activity and, hence, PP i levels, in response to changes in cell energy status ( ATP / ADP ratio).