Emiko Okamura - D-β-aspartyl residue exhibiting uncommon high resistance to spontaneous peptide bond cleavage

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      Publication Details (including relevant citation   information):

      Aki, K. and Okamura, E. Sci. Rep. 6,   21594; doi:10.1038/srep21594 (2016).


      Although L-amino   acids were selected as main constituents of peptides and proteins   during chemical evolution, D-aspartyl (Asp) residue is found in a   variety of living tissues. In particular, D-b-Asp is thought   to be stable than any other Asp isomers, and this could be a   reason for gradual accumulation in abnormal proteins and peptides   to modify their structures and functions. It is predicted that   D-b-Asp shows high   resistance to biomolecular reactions. For instance, less   reactivity of D-b-Asp is expected   to bond cleavage, although such information has not been provided   yet. In this work, the spontaneous peptide bond cleavage was   compared between Asp isomers, by applying real-time   solution-state NMR to eye lens aA-crystallin 51–60   fragment, S51LFRTVLD58SG60  and aB-crystallin 61–67   analog, F61D62TGLSG67 consisting   of L-a-   and D-b-Asp 58 and 62,   respectively. Kinetic analysis showed how tough the uncommon   D-b-Asp residue was   against the peptide bond cleavage as compared to natural   L-a-Asp. Differences   in pKa and conformation between   L-a-   and D-b-Asp side chains   were plausible factors to determine reactivity of Asp isomers.   The present study, for the first time, provides a rationale to   explain less reactivity of D-b-Asp to allow   abnormal accumulation.

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