title: Ground-state electronic destabilization via hyperconjugation in aspartate aminotransferase.
abstract: Binding isotope effects for l-aspartate reacting with the inactive K258A mutant of PLP-dependent aspartate aminotransferase to give a stable external aldimine intermediate are reported. They provide direct evidence for electronic ground-state destabilization via hyperconjugation. The smaller equilibrium isotope effect with deazaPLP-reconstituted K258A indicates that the pyridine nitrogen plays an important role in labilizing the Cα-H bond.
authors.affiliation: Department of Chemistry, University of California - Davis, 95616, United States.
authors.forename: Wait R
authors.initials: WR
authors.lastname: Griswold
authors.forename: Joan Nieto
authors.initials: JN
authors.lastname: Castro
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Fisher
authors.forename: Michael D
authors.initials: MD
authors.lastname: Toney
mesh_terms: D001219:Aspartate Aminotransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001224:Aspartic Acid / Q000378:metabolism*; D002384:Catalysis; D004583:Electrons; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D007097:Imines / Q000378:metabolism; D008958:Models, Molecular; D017354:Point Mutation; D011732:Pyridoxal Phosphate / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D007097:Imines; D001224:Aspartic Acid; D011732:Pyridoxal Phosphate; D001219:Aspartate Aminotransferases