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 drug cuold be developed

Airoldi, C., Sommaruga, S., Merlo, S., Sperandeo, P., Cipolla, L., Polissi, A., et al. (2010). Targeting Bacterial Membranes: NMR Characterization of Substrate Recognition and Binding Requirements of D-arabinose 5P Isomerase, a key enzyme in the biosynthesis of LPS. CHEMISTRY-A EUROPEAN JOURNAL, 16, 1876-1902 [10.1002/chem.200902619].

Targeting Bacterial Membranes: NMR Characterization of Substrate Recognition and Binding Requirements of D-arabinose 5P Isomerase, a key enzyme in the biosynthesis of LPS

AIROLDI, CRISTINA;SPERANDEO, PAOLA;CIPOLLA, LAURA FRANCESCA;POLISSI, ALESSANDRA;NICOTRA, FRANCESCO
2010

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 drug cuold be developed
No
Articolo in rivista - Articolo scientifico
Scientifica
antibiotics,enzymes,inhibitors,isomerization · NMR spectroscopy
English
1876
1902
27
Airoldi, C., Sommaruga, S., Merlo, S., Sperandeo, P., Cipolla, L., Polissi, A., et al. (2010). Targeting Bacterial Membranes: NMR Characterization of Substrate Recognition and Binding Requirements of D-arabinose 5P Isomerase, a key enzyme in the biosynthesis of LPS. CHEMISTRY-A EUROPEAN JOURNAL, 16, 1876-1902 [10.1002/chem.200902619].
Airoldi, C; Sommaruga, S; Merlo, S; Sperandeo, P; Cipolla, L; Polissi, A; Nicotra, F
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/7990
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