Consecutive beta-turn conformation of a synthetic model peptide corresponding to the active site of thioredoxin.
A synthetic model peptide, (formula; see text) which mimics the active-site disulfide loop of thioredoxin has been prepared. 270 MHz 1H-NMR studies establish that Cys-4 and methylamide NH groups are solvent-shielded, using hydrogen-deuterium exchange, solvent and temperature dependence of chemical shifts and nitroxide radical-induced broadening as diagnostic criteria. Infrared measurements provide supporting evidence for intramolecularly hydrogen-bonded conformations. The related peptide in which Gly-2 is replaced by alpha-aminoisobutyric acid has been shown to adopt a similar backbone conformation based on NMR and CD data. Based on the known stereochemical preferences of alpha-aminoisobutyric acid residues, a consecutive beta-turn conformation involving two intramolecular 4 leads to 1 hydrogen bonds is proposed for both disulfides. Vicinal coupling constants and CD data are discussed with reference to the side-chain conformation of the cysteine residues. Large structural differences have been established between the thioredoxin active-site model disulfide and its acyclic precursor.
D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D002942:Circular Dichroism; D004220:Disulfides / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D009842:Oligopeptides / Q000138:chemical synthesis*; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D011487:Protein Conformation; D013055:Spectrophotometry, Infrared; D013879:Thioredoxins / Q000378:metabolism*
D001426:Bacterial Proteins; D004220:Disulfides; D007202:Indicators and Reagents; D009842:Oligopeptides; D010456:Peptides, Cyclic; D013879:Thioredoxins