Empirical rules for rationalising visible circular dichroism of Cu2+ and Ni2+ histidine complexes: applications to the prion protein.
A natively unfolded region of the prion protein, PrP(90-126) binds Cu(2+) ions and is vital for prion propagation. Pentapeptides, acyl-GGGTH(92-96) and acyl-TNMKH(107-111), represent the minimum motif for this Cu(2+) binding region. EPR and (1)H NMR suggests that the coordination geometry for the two binding sites is very similar. However, the visible CD spectra of the two sites are very different, producing almost mirror image spectra. We have used a series of analogues of the pentapeptides containing His(96) and His(111) to rationalise these differences in the visible CD spectra. Using simple histidine-containing tri-peptides we have formulated a set of empirical rules that can predict the appearance of Cu(2+) visible CD spectra involving histidine and amide main-chain coordination.
Klewpatinond
Mark
M
School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, UK.
Viles
John H
JH
D000595:Amino Acid Sequence; D001665:Binding Sites; D002942:Circular Dichroism / Q000592:standards*; D003300:Copper / Q000032:analysis*; D004578:Electron Spin Resonance Spectroscopy; D006639:Histidine / Q000032:analysis*; D009532:Nickel / Q000032:analysis*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry; D011328:Prions / Q000737:chemistry*; D017510:Protein Folding
D009842:Oligopeptides; D011328:Prions; D006639:Histidine; D003300:Copper; D009532:Nickel