title: Human tartrate-resistant acid phosphatase becomes an effective ATPase upon proteolytic activation.
abstract: Proteolytic cleavage in an exposed loop of human tartrate-resistant acid phosphatase (TRAcP) with trypsin leads to a significant increase in activity. At each pH value between 3.25 and 8.0 the cleaved enzyme is more active. Substrate specificity is also influenced by proteolysis. Only the cleaved form is able to hydrolyze unactivated substrates efficiently, and at pH >6 cleaved TRAcP acquires a marked preference for ATP. The cleaved enzyme also has altered sensitivity to inhibitors. Interestingly, the magnitude and mode of inhibition by fluoride depends not only on the proteolytic state but also pH. The combined kinetic data imply a role of the loop residue D158 in catalysis in the cleaved enzyme. Notably, at low pH this residue may act as a proton donor for the leaving group. In this respect the mechanism of cleaved TRAcP resembles that of sweet potato purple acid phosphatase.
authors.affiliation: School of Molecular and Microbial Sciences, The University of Queensland, St. Lucia, Australia.
authors.forename: Natasa
authors.initials: N
authors.lastname: Mitić
authors.forename: Mohsen
authors.initials: M
authors.lastname: Valizadeh
authors.forename: Eleanor W W
authors.initials: EW
authors.lastname: Leung
authors.forename: John
authors.initials: J
authors.lastname: de Jersey
authors.forename: Susan
authors.initials: S
authors.lastname: Hamilton
authors.forename: David A
authors.initials: DA
authors.lastname: Hume
authors.forename: A Ian
authors.initials: AI
authors.lastname: Cassady
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schenk
mesh_terms: D000135:Acid Phosphatase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence; D020134:Catalytic Domain; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D013379:Substrate Specificity; D000071681:Tartrate-Resistant Acid Phosphatase; D014357:Trypsin / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D006493:Heparin; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D014357:Trypsin; D000251:Adenosine Triphosphatases; D005459:Fluorides