Structure determination of LpxA from the lipopolysaccharide-synthesis pathway of Acinetobacter baumannii

Acinetobacter baumannii is a Gram-negative pathogenic bacterium which is resistant to most currently available antibiotics and that poses a significant health threat to hospital patients. LpxA is a key enzyme in the biosynthetic pathway of the lipopolysaccharides that are components of the bacterial outer membrane. It is a potential target for antibacterial agents that might be used to fight A. baumannii infections. This paper describes the structure determination of the apo form of LpxA in space groups P2₁2₁2₁ and P6₃. These crystal forms contained three and one protein molecules in the asymmetric unit and diffracted to 1.8 and 1.4 Å resolution, respectively. A comparison of the conformations of the independent protein monomers within and between the two crystal asymmetric units revealed very little structural variation across this set of structures. In the P6₃ crystal form the enzymatic site is exposed and is available for the introduction of small molecules of the type used in fragment-based drug discovery and structure-based lead optimization.