caa a22 4500 378849719 CHVBK 20180305123320.0 cr unu---uuuuu 161128e20030127xx s 000 0 eng 10.1515/BC.2003.006 doi (NATIONALLICENCE)gruyter-10.1515/BC.2003.006 Different Sensitivities of Mutants and ChimericForms of Human Muscle and Liver Fructose-1,6-Bisphosphatases towards AMP [Elektronische Daten] [D. Rakus, H. Tillmann, R. Wysocki, S. Ulaszewski, K. Eschrich, A. Dzugaj] 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. Copyright © 2003 by Walter de Gruyter GmbH & Co. KG Biochemistry nationallicence Molecular biology nationallicence Cellular biology nationallicence Rakus D. aut Tillmann H. aut Wysocki R. aut Ulaszewski S. aut Eschrich K. aut Dzugaj A. aut Biological Chemistry Walter de Gruyter 384/1(2003-01-27), 51-58 1431-6730 384:1<51 2003 384 bchm https://doi.org/10.1515/BC.2003.006 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1515/BC.2003.006 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rakus D. aut NATIONALLICENCE 700 1- Tillmann H. aut NATIONALLICENCE 700 1- Wysocki R. aut NATIONALLICENCE 700 1- Ulaszewski S. aut NATIONALLICENCE 700 1- Eschrich K. aut NATIONALLICENCE 700 1- Dzugaj A. aut NATIONALLICENCE 773 0- Biological Chemistry Walter de Gruyter 384/1(2003-01-27), 51-58 1431-6730 384:1<51 2003 384 bchm CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter