title: Arabinose 5-phosphate isomerase as a target for antibacterial design: studies with substrate analogues and inhibitors.
abstract: Structural requirements of D-arabinose 5-phosphate isomerase (KdsD, E.C. 5.3.1.13) from Pseudomonas aeruginosa were analysed in detail using advanced NMR techniques. We performed epitope mapping studies of the binding between the enzyme and the most potent KdsD inhibitors found to date, together with studies of a set of newly synthesised arabinose 5-phosphate (A5P) mimetics. We report here the first experimental evidence that KdsD may bind the furanose form of A5P, suggesting that catalysis of ring opening may be an important part of KdsD catalysis.
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Gabrielli
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Merlo
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Airoldi
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Sperandeo
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Gianera
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Polissi
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Nicotra
authors.affiliation: Department of Medicinal Chemistry, University of Michigan, 428 Church Street, Ann Arbor, MI 48109-1065, USA.
authors.forename: Tod P
authors.initials: TP
authors.lastname: Holler
authors.affiliation: Department of Medicinal Chemistry, University of Michigan, 428 Church Street, Ann Arbor, MI 48109-1065, USA. Electronic address: rww@umich.edu.
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Woodard
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy. Electronic address: laura.cipolla@unimib.itUSA.
authors.forename: Laura
authors.initials: L
authors.lastname: Cipolla
mesh_terms: D019747:Aldose-Ketose Isomerases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D007536:Isomerism; D008826:Microbial Sensitivity Tests; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D019747:Aldose-Ketose Isomerases; C041486:arabinose-5-phosphate isomerase
keywords: Enzyme inhibitors; Escherichia coli; Molecular recognition; NMR binding studies; Pseudomonas aeruginosa; d-Arabinose 5-phosphate isomerase