Irreversible inhibition of dihydrodipicolinate synthase by 4-oxo-heptenedioic acid analogues Academic Article uri icon

abstract

  • We report the synthesis of (2E,5E)-4-oxoheptadienedioic acid and (2E)-4-oxoheptenedioic acid and evaluation of both diester and diacid analogues as inhibitors of bacterial dihydrodipicolinate synthase. Enzyme kinetic studies allowed the determination of second-order rate constants of inactivation; and substrate co-incubation studies have shown the inhibitors act at the active-site. Mass spectrometric analyses have further explored the enzyme-inhibitor interaction and determined the sites of enzyme alkylation.

authors

  • Boughton, Berin A
  • Griffin, Michael DW
  • O’Donnell, Paul A
  • Dobson, Renwick CJ
  • Perugini, Matthew A
  • Gerrard, Juliet A
  • Hutton, Craig A

publication date

  • December 2008