Abstract
Helicobacter pylori is a bacterium that can cause chronic active gastritis and peptic ulcer disease. In order to treat H. pylori infection, phosphopantetheine adenylyltransferase (PPAT) involving in coenzyme A (CoA) biosynthesis has been considered as a potential target for antibacterial drug discovery. However, structure of H. pylori PPAT still remains unclear. Here, we report the crystal structures of wild-type and double mutant PPATs. Wild-type PPAT presented as a hexamer and shared a similar structural fold to other heterologous PPATs. Each monomer had 5 β-strands and 4 α-helixes to form a well-packed dinucleotide-binding fold. However, biological assembly of mutant PPAT was a tetramer. The C-terminal 65 residues of mutant PPAT had intimately intertwined with the other polypeptide chain for the dimer formation, which was never found in other PPATs. Mutant PPAT also exhibited significantly differences in thermostability and unfolding behaviors as compared with wild-type PPAT. Functional analysis demonstrated that wild-type and mutant PPATs enabled to bind with CoA and ATP but their binding affinities were distinct.