The diaminopimelate (DAP) biosynthesis pathway occurs in bacteria, plants and some fungi, but is absent in animals, thus offering scope for the discovery of new antibiotics, herbicides and pesticides. The first step of the DAP pathway is a condensation reaction catalysed by the enzyme dihydrodipicolinate synthase (DHDPS), followed then by a reduction reaction catalysed by dihydrodipicolinate reductase (DHDPR). Recent studies suggest that DHDPS and DHDPR form encounter complexes in a species-specific manner. We therefore set out to characterise the structure of DHDPS and DHDPR both in solution and the crystal state from the environmentally- and industrially-important cyanobacterial species, Anabaena variabilis (Av).

Av-DHDPS and Av-DHDPR were successfully cloned, expressed, purified to homogeneity, and crystallised under several different conditions. The structure of A. variabilis DHDPS was subsequently determined to a resolution of 1.9 Å showing the enzyme adopts a typical bacterial ‘head-to-head- homotetramer.  The structure of Av-DHDPR is currently being pursued, as too are the kinetic, hydrodynamic and structural properties of both Av-DHDPS and Av-DHDPR to establish their propensity to form ‘encounter complexes’.

The results of this study offers great potential to afford new knowledge of an exciting class of transient protein-protein interactions (i.e. encounter complexes), and also translational benefits such as the discovery of novel anti-cyanobacterial agents.