Fluoroacetate is a naturally occurring organofluorine compound. An actinomycete,(Streptomyces cattleya), and some plants in Australia and Africa produce this highly toxic compound. Fluoroacetate dehalogenases from Burkholderia sp and Delftia acidovorans catalyze the hydrolytic defluorination of fluoroacetate to produce glycolate. These enzymes are unique in that they catalyze the cleavage of the carbon-fluorine bond, whose dissociation energy is among the highest found in nature. Fluoroacetate is a poison developped as rodenticide
23 structures(e.g. : 6QHT, 6QHQ, 6QHV... more)(less)6QHT: Time resolved structural analysis of the full turnover of an enzyme - 376 ms, 6QHQ: Time resolved structural analysis of the full turnover of an enzyme - 1128 ms, 6QHV: Time resolved structural analysis of the full turnover of an enzyme - 100 ms, 6QHU: Time resolved structural analysis of the full turnover of an enzyme - 100 ms, 6QHX: Time resolved structural analysis of the full turnover of an enzyme - 6156 ms, 6QHW: Time resolved structural analysis of the full turnover of an enzyme - 4512 ms, 6QHZ: Time resolved structural analysis of the full turnover of an enzyme - 6788 ms, 6QHY: Time resolved structural analysis of the full turnover of an enzyme - 100 ms, 6QHS: Time resolved structural analysis of the full turnover of an enzyme - 13536 ms, 6QHP: Time resolved structural analysis of the full turnover of an enzyme - 2256 ms covalent intermediate 1, 6QI1: Time resolved structural analysis of the full turnover of an enzyme - 12312 ms, 6QI0: Time resolved structural analysis of the full turnover of an enzyme - 9024 ms, 6GXT: Rhodopseudomonas palustris Fluoroacetate dehalogenase : FAcD2052MS after reaction initiation, 6GXD: Rhodopseudomonas palustris Fluoroacetate dehalogenase : FAcD752MS after reaction initiation, 4BB0: Structure of a putative epoxide hydrolase Q244E mutant from Pseudomonas aeruginosa, with bound MFA., 4BAU: Structure of a putative epoxide hydrolase T131D mutant from Pseudomonas aeruginosa, with bound MFA., 4B9E: Structure of a putative epoxide hydrolase from Pseudomonas aeruginosa, with bound MFA., 3B12: Crystal Structure of the Fluoroacetate Dehalogenase D104 mutant from Burkholderia sp. FA1 in complex with fluoroacetate, 6QKW: Crystal Structure of the Fluoroacetate Dehalogenase RPA1163 - Tyr219Phe - Fluoroacetate soaked 2hr, 5K3A: Crystal Structure of the Fluoroacetate Dehalogenase RPA1163 - His280Asn/Fluoroacetate - Cocrystallized - Both Protomers Reacted with Ligand, 5K3C: Crystal Structure of the Fluoroacetate Dehalogenase RPA1163 - WT/5-Fluorotryptophan, 3R3V: Crystal Structure of the Fluoroacetate Dehalogenase RPA1163 - Asp110Asn/Fluoroacetate, 3R3Y: Crystal Structure of the Fluoroacetate Dehalogenase RPA1163 - His280Asn/Fluoroacetate
Bacterial infections are increasingly difficult to treat owing to the spread of antibiotic resistance. A major concern is Gram-negative bacteria, for which the discovery of new antimicrobial drugs has been particularly scarce. In an effort to accelerate early steps in drug discovery, the EU-funded AEROPATH project aims to identify novel targets in the opportunistic pathogen Pseudomonas aeruginosa by applying a multidisciplinary approach encompassing target validation, structural characterization, assay development and hit identification from small-molecule libraries. Here, the strategies used for target selection are described and progress in protein production and structure analysis is reported. Of the 102 selected targets, 84 could be produced in soluble form and the de novo structures of 39 proteins have been determined. The crystal structures of eight of these targets, ranging from hypothetical unknown proteins to metabolic enzymes from different functional classes (PA1645, PA1648, PA2169, PA3770, PA4098, PA4485, PA4992 and PA5259), are reported here. The structural information is expected to provide a firm basis for the improvement of hit compounds identified from fragment-based and high-throughput screening campaigns.
