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. Rational design of antibacterial drugs: The identification and characterisation of P. aeruginosa API, which is involved in the biosynthesis of lipopolysaccharides, are reported. Structural requirements for substrate recognition and binding and the effects of mutations of the key residues have been evaluated by STD NMR spectroscopy. This information is essential for the rational design of new potential antibacterial drugs. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Airoldi, C., Sommaruga, S., Merlo, S., Sperandeo, P., Cipolla, L., Polissi, A., et al. (2011). Targeting Bacterial Membranes: Identification of Pseudomonas aeruginosaD-Arabinose-5P Isomerase and NMR Characterisation of its Substrate Recognition and Binding Properties. CHEMBIOCHEM, 12(5), 719-727 [10.1002/cbic.201000754].

Targeting Bacterial Membranes: Identification of Pseudomonas aeruginosaD-Arabinose-5P Isomerase and NMR Characterisation of its Substrate Recognition and Binding Properties

AIROLDI, CRISTINA;MERLO, SILVIA;SPERANDEO, PAOLA;CIPOLLA, LAURA FRANCESCA;POLISSI, ALESSANDRA;NICOTRA, FRANCESCO
2011

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. Rational design of antibacterial drugs: The identification and characterisation of P. aeruginosa API, which is involved in the biosynthesis of lipopolysaccharides, are reported. Structural requirements for substrate recognition and binding and the effects of mutations of the key residues have been evaluated by STD NMR spectroscopy. This information is essential for the rational design of new potential antibacterial drugs. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Articolo in rivista - Articolo scientifico
NMR, LPS, bacteria, API
English
2011
12
5
719
727
none
Airoldi, C., Sommaruga, S., Merlo, S., Sperandeo, P., Cipolla, L., Polissi, A., et al. (2011). Targeting Bacterial Membranes: Identification of Pseudomonas aeruginosaD-Arabinose-5P Isomerase and NMR Characterisation of its Substrate Recognition and Binding Properties. CHEMBIOCHEM, 12(5), 719-727 [10.1002/cbic.201000754].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/20924
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