Crystal Structures of Nucleoside Di Phosphate Kinase From Acinetobacter Baumannii and Pseudomonas Aeruginosa

Abstract

Acinetobacter baumannii and Pseudomonas aeruginosa are responsible for causing life threat infections in hospitals worldwide, ranging in severity from minor skin infections to major infections such as ventilator associated pneumonia . The features such as biofilm formation, serum resistance, motility efflux pumps and iron acquisition mechanisms help the bacterium to survive in adverse environmental conditions and facilitate the development of an infection.Nucleoside diphosphate kinase (NDK) is a housekeeping enzyme responsible for maintaining the NTP pool inside the cell. This enzyme and its homologues are widespread among species and are known to perform diverse functions. NDK was first discovered for its kinase activity however through course of time its other functions were also reported. GTP levels are important for cellular macromolecular synthesis and signalling mechanisms, Ndk plays an important role in bacterial growth, signal transduction and pathogenicity. Specific examples of the role of Ndk in regulating growth, NTP formation and cell surface polysaccharide have been observed in case of other pathogens like Pseudomonas aeruginosa and Mycobacterium tuberculosis. Emerging evidences identifies multiple roles for nucleoside diphosphate kinase in host-microbe interaction which makes it an attractive drug target to combat this pathogen effectively.We have determined crystal structures of NDK from Acinetobacter baumannii and Pseudomonas aeruginosa at 1.98, 1.92, 2.2 angstrom resolutions. The detailed structure analysis reveals presence of mechanisms such as cation binding for stability of structures.The structure of NDK from Pseudomonas aeruginosa and the analysis of active site residues confirms the changes in the active site residues after the cleavage of NDK to make a truncated form which is reponsible for pathogenesis of this bacteria.

Keywords: Acinetobacter baumannii, Pseudomonas aeruginosa, Nucleoside diphosphate kinase (NDK), drug target