Inhibition of phosphate-metabolizing enzymes by oxovanadium(V) complexes.
The chemical similarities between vanadate and phosphate combined with the ability of vanadate to readily undergo changes in coordination geometry allows this ion to strongly influence the function of a large variety of phosphate-metabolizing enzymes. As transition state analogs, spontaneously formed vanadate complexes are potent inhibitors of a number of enzymes, including some ribonucleases, mutases, and phosphatases. In addition, vanadate is an effective inhibitor of many ATPases, kinases, lyases, and synthases. Vanadate oligomers tend to be weaker inhibitors than vanadate but do influence the function of dehydrogenases, mutases, aldolases, kinases, and others. Of the oligomers, decavanadate is unique in that it seems to bind only in polyphosphate binding domains. Peroxovanadate has not yet been well studied but it seems to inhibit enzymes that do not utilize a pentacoordinate vanadate in the catalysis cycle. Additional detailed studies of vanadate-initiated inhibition of enzymes will expand our understanding of the various mechanisms of action of vanadate and its derivatives that have been briefly described here and will doubtless provide insight into other functions of this unique material.
Stankiewicz
P J
PJ
Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
Tracey
A S
AS
Crans
D C
DC
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008190:Lyases / Q000037:antagonists & inhibitors; D010710:Phosphates / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors*; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D012260:Ribonucleases / Q000037:antagonists & inhibitors; D013379:Substrate Specificity; D014638:Vanadates / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D010710:Phosphates; D014638:Vanadates; D010770:Phosphotransferases; D012260:Ribonucleases; D010744:Phosphoric Monoester Hydrolases; D000251:Adenosine Triphosphatases; D008190:Lyases