title: The primordial high energy compound: ATP or inorganic pyrophosphate?
abstract: The pyrophosphate-dependent phosphofructokinase (PP(i)-PFK) of Entamoeba histolytica displays a million fold preference for inorganic pyrophosphate (PP(i)) over ATP (calculated as the ratio of k(cat)/K(m)). The introduction of a single mutation by site-directed mutagenesis changes its preference from PP(i) to ATP. The single mutant has an 8-fold preference for ATP whereas a related double mutant shows a preference exceeding 10,000-fold. The results suggest the presence of a latent nucleotide binding site aligned for a catalytic role in PP(i)-PFK. It is proposed that the ancestral PFK was an ATP-dependent enzyme and that PP(i)-PFKs are a later evolving adaptation.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Chicago Medical School, North Chicago, Illinois 60064, USA.
authors.forename: A
authors.initials: A
authors.lastname: Chi
authors.forename: R G
authors.initials: RG
authors.lastname: Kemp
mesh_terms: D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism*; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D011756:Diphosphates / Q000378:metabolism*; D004734:Energy Metabolism; D004748:Entamoeba histolytica / Q000201:enzymology* / Q000378:metabolism; D019143:Evolution, Molecular; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D011756:Diphosphates; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; C022502:pyrophosphate-fructose 6-phosphate 1-phosphotransferase