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Cysteine 144 Is a Key Residue in the Copper Reduction by the β‐Amyloid Precursor Protein
Author(s) -
Ruiz Francisca H.,
González Mauricio,
Bodini Mario,
Opazo Carlos,
Inestrosa Nibaldo C.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0731288.x
Subject(s) - amyloid precursor protein , peptide , cysteine , chemistry , mutant , beta (programming language) , copper , amino acid , amyloid beta , biochemistry , enzyme , alzheimer's disease , gene , medicine , disease , organic chemistry , pathology , computer science , programming language
: The β‐amyloid precursor protein (β‐APP) contains a copper‐binding site localized between amino acids 135 and 156 (β‐APP 135‐156 ). We have employed synthetic β‐APP peptides to characterize their capacities to reduce Cu(II) to Cu(I). Analogues of the wild‐type β‐APP 135‐156 peptide, containing specific amino acid substitutions, were used to establish which residues are specifically involved in the reduction of copper by β‐APP 135‐156 . We report here that β‐APP’s copper‐binding domain reduced Cu(II) to Cu(I). The single‐mutant β‐APP His147→Ala and the double‐mutant β‐APP His147→Ala/His149→Ala showed a small decrease in copper reduction in relation to the wild‐type peptide and the β‐APP Sys144→Ser mutation abolished it, suggesting that Cys 144 is the key amino acid in the oxidoreduction reaction. Our results confirm that soluble β‐APP is involved in the reduction of Cu(II) to Cu(I).