title: Insights into internal dynamics of 6-phosphogluconolactonase from Trypanosoma brucei studied by nuclear magnetic resonance and molecular dynamics.
abstract: Nuclear magnetic resonance is used to investigate the backbone dynamics in 6-phosphogluconolactonase from Trypanosoma brucei (Tb6PGL) with (holo-) and without (apo-) 6-phosphogluconic acid as ligand. Relaxation data were analyzed using the model-free approach and reduced spectral density mapping. Comparison of predictions, based on 77 ns molecular dynamics simulations, with the observed relaxation rates gives insight into dynamical properties of the protein and their alteration on ligand binding. Data indicate dynamics changes in the vicinity of the binding site. More interesting is the presence of perturbations located in remote regions of this well-structured globular protein in which no large-amplitude motions are involved. This suggests that delocalized changes in dynamics that occur upon binding could be a general feature of protein-target interactions.
authors.affiliation: Département de Chimie, Ecole Normale Supérieure, Paris, France.
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Calligari
authors.forename: Gilmar F
authors.initials: GF
authors.lastname: Salgado
authors.forename: Philippe
authors.initials: P
authors.lastname: Pelupessy
authors.forename: Philippe
authors.initials: P
authors.lastname: Lopes
authors.forename: Jamal
authors.initials: J
authors.lastname: Ouazzani
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Bodenhausen
authors.forename: Daniel
authors.initials: D
authors.lastname: Abergel
mesh_terms: D001665:Binding Sites; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry*; D019295:Computational Biology; D005942:Gluconates / Q000737:chemistry; D020035:Holoenzymes / Q000737:chemistry; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D025341:Principal Component Analysis; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017433:Protein Structure, Secondary; D015800:Protozoan Proteins / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014346:Trypanosoma brucei brucei / Q000737:chemistry / Q000201:enzymology*
chemical_list: D005942:Gluconates; D020035:Holoenzymes; D008024:Ligands; D015800:Protozoan Proteins; D002265:Carboxylic Ester Hydrolases; C022363:6-phosphogluconolactonase; C008884:6-phosphogluconic acid