Structural effects of Cu(II)-coordination in the octapeptide region of the human prion protein.
The copper-binding ability of the prion protein is thought to be central to its function. The structural effects of copper coordination in the octapeptide region of the human prion protein have been investigated by molecular dynamics simulations. Simulations were performed with the apo state, in order to investigate the behavior of the region without copper ions, as well as with the octapeptide region in the presence of copper ions. While the structure of the apo state is greatly influenced by the interaction between the rings in the histidine, tryptophan and proline residues, the region shows evidence of highly ordered coordination sites in the presence of copper ions. The position of the tryptophan indole ring is stabilized by cation-pi interactions. Two stable orientations of the indole ring with respect to the equatorial coordination plane of copper were observed, which showed that the indole ring can reside on both sides of the coordination plane. The interaction with the indole ring was found to occur without a mediating axial water molecule.
Riihimäki
Eva-Stina
ES
Inorganic Chemistry, Department of Chemistry, Royal Institute of Technology, 100 44, Stockholm, Sweden.
Martínez
José Manuel
JM
Kloo
Lars
L
D003300:Copper / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D011328:Prions / Q000737:chemistry*; D011485:Protein Binding / Q000187:drug effects; D012399:Rotation; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry
D009842:Oligopeptides; D011328:Prions; D003300:Copper; D014364:Tryptophan