Emiko Okamura - Kinetics of the competitive reactions of isomerization and peptide bond cleavage at L-α- and D-β-aspartyl residues in an αA-crystallin fragment

Document created by Emiko Okamura on Jun 15, 2017Last modified by Emiko Okamura on Sep 28, 2017
Version 2Show Document
  • View in full screen mode

  Publication Details (including relevant citation   information):

  Aki, K. and Okamura, E. J. Pept.Sci.2017;23:2837


  D-β-aspartyl (Asp) residue has been found in a   living body such as aged lens crystallin, although l-α-amino acids are constituents in natural   proteins. Isomerization from l-α-   to d-β-Asp probably modulates   structures to affect biochemical reactions. At Asp residue,   isomerization and peptide bond cleavage compete with each other.   To gain insight into how fast each reaction proceeds, the   analysis requires the consideration of both pathways   simultaneously and independently. No information has been   provided, however, about these competitive processes because each   reaction has been studied separately. The contribution of Asp   isomers to the respective pathways has still been veiled. In this   work, the two competitive reactions, isomerization and   spontaneous peptide bond cleavage at Asp residue, were   simultaneously observed and compared in an αA-crystallin   fragment, S51LFRTVLD58SG60 containing l-α- and d-β-Asp58 isomers. The kinetics showed that   the formation of l- and   d-succinimide (Suc) intermediate,   as a first step of isomerization, was comparable at l-α- and d-β-Asp. Although l-Suc was converted to l-β-Asp, d-Suc   was liable to return to the original d-β-Asp, the reverse reaction marked enough to   consider d-β-Asp as apparently   stable. d-β-Asp was also resistant   to the peptide bond cleavage. Such apparent less reactivity is   probably the reason for gradual and abnormal accumulation of   d-β-Asp in a living body under   physiological conditions. 

  Address (URL): http://onlinelibrary.wiley.com/doi/10.1002/psc.2945/full