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Targeting Bacterial Membranes: Identification of Pseudomonas aeruginosa D ‐Arabinose‐5P Isomerase and NMR Characterisation of its Substrate Recognition and Binding Properties
Author(s) -
Airoldi Cristina,
Sommaruga Silvia,
Merlo Silvia,
Sperandeo Paola,
Cipolla Laura,
Polissi Alessandra,
Nicotra Francesco
Publication year - 2011
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201000754
Subject(s) - isomerase , pseudomonas aeruginosa , biochemistry , chemistry , bacteria , antibacterial activity , substrate (aquarium) , stereochemistry , rational design , enzyme , biology , genetics , ecology
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.