Irreversible inhibition of dihydrodipicolinate synthase by 4-oxo-heptenedioic acid analogues |
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Authors: | Boughton Berin A Griffin Michael D W O'Donnell Paul A Dobson Renwick C J Perugini Matthew A Gerrard Juliet A Hutton Craig A |
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Affiliation: | School of Chemistry, University of Melbourne, Parkville, Vic. 3010, Australia. |
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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. |
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