Emiko Okamura - Staggered side-chain conformers of aspartyl residues prerequisite to transformation from L-α- to D-β-aspartate 58 in human-lens αA-crystallin fragment

Document created by Emiko Okamura on May 28, 2015Last modified by Emiko Okamura on Apr 14, 2016
Version 2Show Document
  • View in full screen mode

  Publication Details (including relevant citation   information):

     K. Aki,E. Okamura,Biophys. Chem.,196, 10-15   (2015).    

  Abstract:

    D-b-aspartyl   (Asp) residues are found in aged human-lens   aA-crystallin.   To explore why the uncommon D-b-Asp   is accumulated, the stability of L-a-,   D-a-,   and D-b-Asp   residues is compared in view of the staggered side-chain   conformers. By using   aA-crystallin   fragment, T55VLD58SGISEVR65,   composed of Asp58 isomers, the vicinal spin-spin coupling   constants of Asp58 Ha-Hb1    and Ha-Hb2    are quantified by high-resolution solution NMR. The trans   conformer is most preferred in the D-b-Asp   side-chain, whereas gauche+ and gauche- are abundant in   L-a-   and D-a-Asp.   The close distance between Asp58 carboxylate carbon   (CCOO-) and Ser59 nitrogen   (N) in gauche+ and gauche- is advantageous to   the intramolecular cyclization to form succinimide intermediate,   followed by the transformation from   a-   to   b-Asp.   The cyclization is not allowed in the trans conformer because of   the long distance between CCOO- and   N, to keep D-b-Asp   stable. The change from gauche to trans conformer in   D-b-Asp   is exothermic and enthalpy-driven.

  Address (URL):

 

Attachments

    Outcomes