Targeting bacterial membranes: NMR spectroscopy characterization of substrate recognition and binding requirements of D-arabinose-5-phosphate isomerase
Articolo
Data di Pubblicazione:
2010
Citazione:
Targeting bacterial membranes: NMR spectroscopy characterization of substrate recognition and binding requirements of D-arabinose-5-phosphate isomerase / C. Airoldi, S. Sommaruga, S. Merlo, P. Sperandeo, L. Cipolla, A. Polissi, F. Nicotra. - In: CHEMISTRY-A EUROPEAN JOURNAL. - ISSN 0947-6539. - 16:6(2010 Feb 08), pp. 1897-1902.
Abstract:
Lipopolysaccharide (LPS) is an essential component of the outer membrane of gram-negative bacteria and consists of three elements: lipid A, the core oligosaccharide, and the O-antigen. The inner-core region is highly conserved and contains at least one residue of 3-deoxy-D-manno-octulosonate (Kdo). Arabinose-5-phosphate isomerase (API) is an aldo-keto isomerase catalyzing the reversible isomerization of D-ribulose-5-phosphate (Ru5P) to D-arabinose-5-phosphate (A5P), the first step of Kdo biosynthesis. By exploiting saturation transfer difference (STD) NMR spectroscopy, the structural requirements necessary for API substrate recognition and binding were identified, with the aim of designing new API inhibitors. In addition, simple experimental conditions for the STD experiments to perform a fast, robust, and efficient screening of small libraries of potential API inhibitors, allowing the identification of new potential leads, were set up. Due to the essential role of API enzymes in LPS biosynthesis and gram-negative bacteria survival, by exploiting these data, a new generation of potent antibacterial drugs could be developed.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Aldose-Ketose Isomerases; Binding Sites; Escherichia coli; Isomerism; Lipopolysaccharides; Magnetic Resonance Spectroscopy; Membranes; O Antigens; Polysaccharides, Bacterial; Substrate Specificity; Sugar Acids
Elenco autori:
C. Airoldi, S. Sommaruga, S. Merlo, P. Sperandeo, L. Cipolla, A. Polissi, F. Nicotra
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