Molecular adaptation and allostery in plant pantothenate synthetases.
Pantothenate synthetase catalyzes the ATP-dependent condensation of pantoate and beta-alanine to yield pantothenate, the essential precursor to coenzyme A. Bacterial and plant pantothenate synthetases are dimeric enzymes that share significant sequence identity. Here we show that the two-step reaction mechanism of pantothenate synthetase is conserved between the enzymes from Arabidopsis thaliana and Escherichia coli. Strikingly, though, the Arabidopsis enzyme exhibits large allosteric effects, whereas the Escherichia coli enzyme displays essentially non-allosteric behavior. Our data suggest that specific subunit contacts were selected and maintained in the plant lineage of the pantothenate synthetase protein family and that the resulting allosteric interactions are balanced for efficient catalysis at low pantoate levels. This is supported by mutations in the putative subunit interface of Arabidopsis pantothenate synthetase, which strongly attenuated or otherwise modified its allosteric properties but did not affect the dimeric state of the enzyme. At the molecular level, plant pantothenate synthetases exemplify functional adaptation through allostery and without alterations to the active site architecture. We propose that the allosteric behavior confers a selective advantage in the context of the subcellular compartmentation of pantothenate biosynthesis in plants.
Jonczyk
Rafal
R
Lehrstuhl für Genetik, Technische Universität München, 85350 Freising, Germany.
Genschel
Ulrich
U
D000222:Adaptation, Physiological; D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D017360:Arabidopsis / Q000201:enzymology / Q000235:genetics; D001483:Base Sequence; D020134:Catalytic Domain / Q000235:genetics; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000235:genetics; D018744:DNA, Plant / Q000235:genetics; D019281:Dimerization; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation; D010453:Peptide Synthases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010944:Plants / Q000201:enzymology* / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D018076:DNA, Complementary; D018744:DNA, Plant; D010453:Peptide Synthases; C022318:pantothenate synthetase