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

被引：31

作者：

Airoldi, Cristina ^{[1
]}

Sommaruga, Silvia ^{[1
]}

Merlo, Silvia ^{[1
]}

Sperandeo, Paola ^{[1
]}

Cipolla, Laura ^{[1
]}

Polissi, Alessandra ^{[1
]}

Nicotra, Francesco ^{[1
]}

机构：

[1] Univ Milano Bicocca, Dept Biosci & Biotechnol, I-20126 Milan, Italy

来源：

CHEMBIOCHEM | 2011年 / 12卷 / 05期

关键词：

antibiotics; enzymes; inhibitors; isomerization; NMR binding studies; TRANSFER-DIFFERENCE NMR; UDP-GALACTOPYRANOSE MUTASE; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; LIGAND-BINDING; LIPOPOLYSACCHARIDE; SPECTROSCOPY; BIOSYNTHESIS; MECHANISM; 5-PHOSPHATE;

D O I：

10.1002/cbic.201000754

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 wildtype 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.

引用

页码：719 / 727

页数：9

共 41 条

[1] Synthesis of 3-Deoxy-d-threopentofuranose 5-Phosphate, a Substrate of Arabinose 5-Phosphate Isomerase [J].