NR AVYM
AU Ronga,L.; Langella,E.; Palladino,P.; Marasco,D.; Tizzano,B.; Saviano,M.; Pedone,C.; Improta,R.; Ruvo,M.
TI Does tetracycline bind helix 2 of prion? An integrated spectroscopical and computational study of the interaction between the antibiotic and alpha helix 2 human prion protein fragments
QU Proteins 2007 Feb 15; 66(3): 707-15
PT journal article; research support, non-u.s. gov't
AB We demonstrate here that tetracycline (TC) can strongly interact (KD' = 189 +/- 7 nM) with model peptides derived from the C-terminal globular domain of the prion protein, hPrP [173-195], and that interaction concerns residues within the C-terminal half of the helix 2, a short region previously indicated as endowed with ambivalent conformational behavior and implicated in PrP conversion to the beta-sheet-rich, infective scrapie variant. Data have been confirmed by binding studies with the N-terminal truncated 180-195 variant that displays a dissociation constant of 483 +/- 30 nM. Remarkably, TC does not influence the structure of the N-terminally fluoresceinated peptides that both show alpha-helical conformations. Docking calculations and molecular dynamics simulations suggest a direct, strong interaction of the antibiotic with exposed side chain functional groups of threonines 190-193 on the solvent-exposed surface of helix 2.
MH Amino Acid Sequence; Anti-Bacterial Agents/chemistry; Circular Dichroism; Humans; Kinetics; Molecular Sequence Data; Peptides/chemical synthesis/chemistry/isolation & purification; Prions/chemistry/*metabolism; Protein Binding; Protein Conformation; Solvents; Spectrometry, Fluorescence; Tetracycline/chemistry/*metabolism
AD Istituto di Biostrutture e Bioimmagini del CNR, Sezione Biostrutture, via Mezzocannone 16, 80134 Napoli, Italy.
SP englisch
PO USA