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D. Rakus, H. Tillmann, R. Wysocki, S. Ulaszewski, K. Eschrich, A. Dzugaj
Different Sensitivities of Mutants and Chimeric Forms of Human Muscle and Liver Fructose- 1,6-Bisphosphatases towards AMP
AMP is an allosteric inhibitor of human muscle and liver fructose-1,6-bisphosphatase (FBPase). Despite strong similarity of the nucleotide binding domains, the muscle enzyme is inhibited by AMP approximately 35 times stronger than liver FBPase: I0.5 for muscle and for liver FBPase are 0.14 uM and 4.8 uM, respectively. Chimeric human muscle (L50M288) and chimeric human liver enzymes (M50L288), in which the N-terminal residues (1-50) were derived from the human liver and human muscle FBPases, respectively, were inhibited by AMP 2-3 times stronger than the wild-type liver enzyme. An amino acid exchange within the Nterminal region of the muscle enzyme towards liver FBPase (Lys20?Glu) resulted in 13-fold increased I0.5 values compared to the wild-type muscle enzyme. However, the opposite exchanges in the liver enzyme (Glu20?Lys and double mutation Glu19?Asp/Glu20?Lys) did not change the sensitivity for AMP inhibition of the liver mutant (I0.5 value of 4.9 uM). The decrease of sensitivity for AMP of the muscle mutant Lys20?Glu, as well as the lack of changes in the inhibition by AMP of liver mutants Glu20?Lys and Glu19?Asp/Glu20?Lys, suggest a different mechanism of AMP binding to the muscle and liver enzyme.
Biological Chemistry, Walter de Gruyter
Print ISSN: 1431-6730
Volume: 384, 01/2003
Pages: 51 - 58