Publication Details (including relevant citation information):
K. Aki,E. Okamura,Biophys. Chem.,196, 10-15 (2015).
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.