title: Selective inhibition of 6-phosphogluconate dehydrogenase from Trypanosoma brucei.
abstract: A number of triphenylmethane derivatives have been screened against 6-phosphogluconate dehydrogenase from Trypanosoma brucei and sheep liver. Some of these compounds show good inhibition of the enzymes and also selectivity towards the parasite enzyme. Modelling was undertaken to dock the compounds into the active sites of both enzymes. Using a combination of DOCK 3.5 and FLEXIDOCK a correlation was obtained between docking score and both activity for the enzymes and selectivity. Visualisation of the docked structures of the inhibitors in the active sites of the enzymes yielded a possible explanation of the selectivity for the parasite enzyme.
authors.affiliation: Dipartimento di Biochimica e Biologia molecolare, Universita di Ferrara, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bertelli
authors.forename: E
authors.initials: E
authors.lastname: El-Bastawissy
authors.forename: M H
authors.initials: MH
authors.lastname: Knaggs
authors.forename: M P
authors.initials: MP
authors.lastname: Barrett
authors.forename: S
authors.initials: S
authors.lastname: Hanau
authors.forename: I H
authors.initials: IH
authors.lastname: Gilbert
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D003198:Computer Simulation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008958:Models, Molecular; D010734:Phosphogluconate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D012984:Software; D014346:Trypanosoma brucei brucei / Q000201:enzymology*
chemical_list: D004791:Enzyme Inhibitors; D010734:Phosphogluconate Dehydrogenase