PMID- 10461923 OWN - NLM STAT- MEDLINE DCOM- 19990914 LR - 20190630 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 73 IP - 3 DP - 1999 Sep TI - Cysteine 144 is a key residue in the copper reduction by the beta-amyloid precursor protein. PG - 1288-92 AB - The beta-amyloid precursor protein (beta-APP) contains a copper-binding site localized between amino acids 135 and 156 (beta-APP(135-156)). We have employed synthetic beta-APP peptides to characterize their capacities to reduce Cu(II) to Cu(I). Analogues of the wild-type beta-APP(135-156) peptide, containing specific amino acid substitutions, were used to establish which residues are specifically involved in the reduction of copper by beta-APP(135-156). We report here that beta-APP's copper-binding domain reduced Cu(II) to Cu(I). The single-mutant beta-APP(His147-->Ala) and the double-mutant beta-APP(His147-->Ala/His149-->Ala) showed a small decrease in copper reduction in relation to the wild-type peptide and the beta-APP(Cys144-->Ser) mutation abolished it, suggesting that Cys144 is the key amino acid in the oxidoreduction reaction. Our results confirm that soluble beta-APP is involved in the reduction of Cu(II) to Cu(I). FAU - Ruiz, F H AU - Ruiz FH AD - Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Santiago, Chile. FAU - Gonzalez, M AU - Gonzalez M FAU - Bodini, M AU - Bodini M FAU - Opazo, C AU - Opazo C FAU - Inestrosa, N C AU - Inestrosa NC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Peptide Fragments) RN - 789U1901C5 (Copper) RN - K848JZ4886 (Cysteine) SB - IM MH - Amino Acid Substitution MH - Amyloid beta-Protein Precursor/*chemistry MH - Copper/*chemistry MH - Cysteine/*chemistry MH - Humans MH - Mutation MH - Oxidation-Reduction MH - Peptide Fragments/chemistry MH - Potentiometry EDAT- 1999/08/26 00:00 MHDA- 1999/08/26 00:01 CRDT- 1999/08/26 00:00 PHST- 1999/08/26 00:00 [pubmed] PHST- 1999/08/26 00:01 [medline] PHST- 1999/08/26 00:00 [entrez] AID - 10.1046/j.1471-4159.1999.0731288.x [doi] PST - ppublish SO - J Neurochem. 1999 Sep;73(3):1288-92. doi: 10.1046/j.1471-4159.1999.0731288.x.