title: 1,3-Phenylene bis(ketoacid) derivatives as inhibitors of Escherichia coli dihydrodipicolinate synthase.
abstract: Dihydrodipicolinate synthase is a key enzyme in the lysine biosynthesis pathway that catalyzes the condensation of pyruvate and aspartate semi-aldehyde. A series of phenolic ketoacid derivatives that mimic the proposed enzymatic intermediate were designed as potential inhibitors of this enzyme and were synthesized from simple precursors. The ketoacid derivatives were shown to act as slow and slow-tight binding inhibitors. Mass spectrometric experiments provided further evidence to support the proposed model of inhibition, demonstrating either an encounter complex or a condensation product for the slow and slow-tight binding inhibitors, respectively.
authors.affiliation: School of Chemistry, The University of Melbourne, VIC 3010, Australia.
authors.forename: Berin A
authors.initials: BA
authors.lastname: Boughton
authors.forename: Lilian
authors.initials: L
authors.lastname: Hor
authors.forename: Juliet A
authors.initials: JA
authors.lastname: Gerrard
authors.forename: Craig A
authors.initials: CA
authors.lastname: Hutton
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006836:Hydro-Lyases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007651:Keto Acids / Q000138:chemical synthesis / Q000737:chemistry*; D007700:Kinetics; D013058:Mass Spectrometry
chemical_list: D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D007651:Keto Acids; D006836:Hydro-Lyases; C020040:4-hydroxy-tetrahydrodipicolinate synthase