Isocitrate dehydrogenase kinase/phosphatase exhibits an intrinsic adenosine triphosphatase activity.
In Escherichia coli, isocitrate dehydrogenase (IDH) is regulated by reversible phosphorylation. The bifunctional enzyme which catalyzes this phosphorylation cycle, IDH kinase/phosphatase, also exhibits a specific ATPase activity. Mutant derivatives of this protein which are nearly devoid of IDH phosphatase activity retain both IDH kinase and ATPase activity, indicating that ATP hydrolysis does not result from the cyclic phosphorylation of IDH. However, the IDH kinase and ATPase activities of these mutant proteins differ significantly from those of the wild-type IDH kinase/phosphatase expressed from the parental allele. This observation suggest that IDH kinase and IDH phosphatase do not reside on structurally independent domains. In contrast to many enzymes which catalyze kinetically unfavorable side reactions, the maximum velocity of the ATPase substantially exceeded those of IDH kinase and IDH phosphatase. ATP hydrolysis was only partially inhibited by phospho- and dephospho-IDH, with saturating levels of phospho-IDH decreasing the rate of ATP hydrolysis by a factor of approximately 5. Even in the presence of near-saturating concentrations of phospho-IDH, the rate of ATP hydrolysis was 4-fold greater than the rate of the cyclic phosphorylation of IDH.
Stueland
C S
CS
Department of Biochemistry, University of Minnesota, Minneapolis 55455.
Eck
K R
KR
Stieglbauer
K T
KT
LaPorte
D C
DC
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D007700:Kinetics; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases
D007521:Isocitrate Dehydrogenase; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C042301:isocitrate dehydrogenase kinase; C042300:isocitrate dehydrogenase phosphatase; D010749:Phosphoprotein Phosphatases; D000251:Adenosine Triphosphatases