TY - JOUR
T1 - Phosphorylation inactivates Escherichia coli isocitrate dehydrogenase by preventing isocitrate binding
AU - Dean, A. M.
AU - Lee, M. H I
AU - Koshland, D. E.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1989
Y1 - 1989
N2 - Equilibrium binding studies demonstrate that purified Escherichia coli isocitrate dehydrogenase binds isocitrate, α-ketoglutarate, NADP, and NADPH at 1:1 ratios of substrate to enzyme monomer. The phosphorylated enzyme, which is completely inactive, is unable to bind isocitrate but retains the ability to bind NADP and NADPH. Replacement of serine 113, which is the site of phosphorylation, by aspartate results in an inactive enzyme that is unable to bind isocitrate. Replacement of the same serine with other amino acids (lysine, threonine, cysteine, tyrosine, and alanine) produces active enzymes that bind both substrates. Hence, the negative charge of an aspartate or a phosphorylated serine at site 113 inactivates the enzyme by preventing the binding of isocitrate.
AB - Equilibrium binding studies demonstrate that purified Escherichia coli isocitrate dehydrogenase binds isocitrate, α-ketoglutarate, NADP, and NADPH at 1:1 ratios of substrate to enzyme monomer. The phosphorylated enzyme, which is completely inactive, is unable to bind isocitrate but retains the ability to bind NADP and NADPH. Replacement of serine 113, which is the site of phosphorylation, by aspartate results in an inactive enzyme that is unable to bind isocitrate. Replacement of the same serine with other amino acids (lysine, threonine, cysteine, tyrosine, and alanine) produces active enzymes that bind both substrates. Hence, the negative charge of an aspartate or a phosphorylated serine at site 113 inactivates the enzyme by preventing the binding of isocitrate.
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M3 - Article
C2 - 2511204
AN - SCOPUS:0024380864
SN - 0021-9258
VL - 264
SP - 20482
EP - 20486
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 34
ER -