NR AVCX
AU Cox,D.L.; Pan,J.; Singh,R.R.P.
TI A mechanism for copper inhibition of infectious prion conversion
QU Biophysical Journal 2006 Jul 15; 91(2): L11-3
PT letter
AB We employ ab initio electronic structure calculations to obtain two structural models for copper bound in the strongest binding site of the noninfectious form of the prion protein. The models are compatible with available experimental constraints from electron spin resonance data. The bending of the peptide backbone attendant with the copper binding is not compatible with the requisite straight beta-strand backbone structure for the same sequence contained in two recently proposed models of the prion protein structure in its infectious form. We hypothesize that copper binding at this site is protective against conversion to the infectious form, discuss experimental data that appear to support and conflict with our hypothesis, and propose tests using recombinant prion protein, genetically modified cultured neurons, and transgenic mice.
MH Animals; Binding Sites; Copper/*metabolism; Humans; Mice; *Models, Molecular; PrPc Proteins/*metabolism; PrPsc Proteins/*metabolism; Protein Binding; Protein Conformation; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
SP englisch
PO USA