Conformational analysis of amyloid precursor protein fragment containing amino acids 667-676, and the effect of D-Asp and iso-Asp substitution at Asp₆₇₂ residue.
Amyloid precursor protein (APP) fragment containing amino acids 667-676, (APP₆₆₇₋₆₇₆), is a substrate for β-secretase which is responsible for generating amyloid β peptides. Conformational analysis of APP₆₆₇₋₆₇₆ peptide [Ac-Ser-Glu-Val-Lys-Met-Asp-Ala-Glu-Phe-Arg-NH₂] and the effect of substitution of Asp₆₇₂ with D-Asp and iso-L-Asp, studied for the first time, demonstrate that the peptide backbone of APP₆₆₇₋₆₇₆ is flexible and adopts different conformations in different solvent environments (water, trifluoroethanol and dimethylsulfoxide). A major conformational difference was observed in trifluoroethanol solvent when Asp₆₇₂ is substituted with D-Asp and iso-Asp. These conformational changes involved in APP₆₆₇₋₆₇₆ may assist in understanding the interactions between β-secretase and APP₆₆₇₋₆₇₆, with relevance to Alzheimer's disease.
Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA.
Ganesh
G
Shanmugam
Prasad L
PL
Polavarapu
Emma
E
Láng
Zsuzsa
Z
Majer
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry*; D002942:Circular Dichroism; D008969:Molecular Sequence Data; D011487:Protein Conformation
D000596:Amino Acids; D016564:Amyloid beta-Protein Precursor