Computational Investigation of Bisphosphate Inhibitors of 3-Deoxy-d--octulosonate 8-phosphate Synthase.

The synthase, 3-deoxy-d--octulosonate 8-phosphate (KDO8P), is a key enzyme for the lipopolysaccharide (LPS) biosynthesis of gram-negative bacteria and a potential target for developing new antimicrobial agents. In this study, computational molecular modeling methods were used to determine the complete structure of the KDO8P synthase from and to investigate the molecular mechanism of its inhibition by three bisphosphate inhibitors: BPH1, BPH2, and BPH3. Our results showed that BPH1 presented a protein-ligand complex with the highest affinity, which is in agreement with experimental data.