Characterisation of dihydrodipicolinate synthase (DHDPS) from Bacillus anthracis.

摘要: Abstract Bacillus anthracis is a Gram-positive spore-forming bacterium that the causative agent of anthrax disease. The use as bioweapon has increased pressure for development an effective treatment. Dihydrodipicolinate synthase (DHDPS) catalyses first committed step in biosynthetic pathway yielding two essential bacterial metabolites, meso-diaminopimelate (DAP) and (S)-lysine. DHDPS therefore potential antibiotic target, microbes require either lysine or DAP component cell wall. This paper biochemical description from B. anthracis. Enzyme kinetic analyses, isothermal titration calorimetry (ITC), mass spectrometry differential scanning fluorimetry (DSF) were used to characterise compare it with well characterised Escherichia coli enzyme. exhibited different behaviour compared E. DHDPS, particular, substrate inhibition by (S)-aspartate semi-aldehyde was observed enzyme (Ksi(ASA) = 5.4 ± 0.5 mM), but not As predicted comparison X-ray crystal structures, inhibited lysine. thermally stabilised substrate, pyruvate, greater extent than its counterpart, weaker affinity pyruvate based on kinetics ITC studies. characterisation will provide useful information design inhibitors new antibiotics targeting