Inhibition of phosphatase and sulfatase by transition-state analogues.
The inhibition constants for vanadate, chromate, molybdate, and tungstate have been determined with Escherichia coli alkaline phosphatase, potato acid phosphatase, and Helix pomatia aryl sulfatase. Vanadate was a potent inhibitor of all three enzymes. Inhibition of both phosphatases followed the order WO4(2-) greater than MoO4(2-) greater than CrO4(2-). The Ki values for potato acid phosphatase were about 3 orders of magnitude lower than those for alkaline phosphatase. Aryl sulfatase followed the reverse order of inhibition by group VI oxyanions. Phenol enhanced inhibition of alkaline phosphatase by vanadate and chromate but did not affect inhibition of acid phosphatase. Phenol enhanced inhibition of aryl sulfatase by metal oxyanions in all cases following the order H2VO4- greater than CrO4(2-) greater than MoO4(2-) greater than WO4(2-), and N-acetyltyrosine ethyl ester enhanced inhibition of aryl sulfatase by H2VO4- and CrO4(2-) more strongly than did phenol. It is apparent that the effectiveness of metal oxyanions as inhibitors of phosphatases and sulfatases can be selectively enhanced in the presence of other solutes. The relevance of these observations to the effects of transition metal oxyanions on protein phosphatases in vivo is discussed.
Stankiewicz
P J
PJ
Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
Gresser
M J
MJ
D000135:Acid Phosphatase / Q000037:antagonists & inhibitors*; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors*; D000818:Animals; D001192:Arylsulfatases / Q000037:antagonists & inhibitors*; D001665:Binding Sites; D002840:Chromates / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D006372:Helix, Snails / Q000201:enzymology; D007700:Kinetics; D008982:Molybdenum / Q000494:pharmacology*; D010944:Plants / Q000201:enzymology; D011485:Protein Binding; D013429:Sulfatases / Q000037:antagonists & inhibitors*; D014414:Tungsten / Q000494:pharmacology*; D017973:Tungsten Compounds; D014638:Vanadates / Q000494:pharmacology*
D002840:Chromates; D017973:Tungsten Compounds; C044659:molybdate; D014638:Vanadates; D008982:Molybdenum; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D013429:Sulfatases; D001192:Arylsulfatases; C045951:tungstate; D014414:Tungsten