title: Targeting bacterial membranes: identification of Pseudomonas aeruginosa D-arabinose-5P isomerase and NMR characterisation of its substrate recognition and binding properties.
abstract: The identification and characterisation of Pseudomonas aeruginosa KdsD (Pa-KdsD), a D-arabinose-5P isomerase involved in the biosynthesis of 3-deoxy-D-manno-oct-2-ulosonic acid and thus of lipopolysaccharide (LPS), are reported. We have demonstrated that KdsD is essential for P. aeruginosa survival and thus represents a key target for the development of novel antibacterial drugs. The key amino acid residues for protein activity have been identified. The structural requirements for substrate recognition and binding have been characterised for the wild-type protein, and the effect of mutations of the key residues on catalytic activity and binding have been evaluated by saturation transfer difference (STD) NMR spectroscopy. Our data provide important structural information for the rational design of new KdsD inhibitors as potential antibacterial drugs.
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Airoldi
authors.forename: Silvia
authors.initials: S
authors.lastname: Sommaruga
authors.forename: Silvia
authors.initials: S
authors.lastname: Merlo
authors.forename: Paola
authors.initials: P
authors.lastname: Sperandeo
authors.forename: Laura
authors.initials: L
authors.lastname: Cipolla
authors.forename: Alessandra
authors.initials: A
authors.lastname: Polissi
authors.forename: Francesco
authors.initials: F
authors.lastname: Nicotra
mesh_terms: D019747:Aldose-Ketose Isomerases / Q000235:genetics / Q000378:metabolism*; D005798:Genes, Bacterial; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D019747:Aldose-Ketose Isomerases; C041486:arabinose-5-phosphate isomerase