title: Staggered side-chain conformers of aspartyl residues prerequisite to transformation from L-α- to D-β-aspartate 58 in human-lens αA-crystallin fragment.
abstract: D-β-aspartyl (Asp) residues are found in aged human-lens αA-crystallin. To explore why the uncommon D-β-Asp is accumulated, the stability of L-α-, D-α-, and D-β-Asp residues is compared in view of the staggered side-chain conformers. By using αA-crystallin fragment, T(55)VLD(58)SGISEVR(65), composed of Asp58 isomers, the vicinal spin-spin coupling constants of Asp58 Hα-Hβ1 and Hα-Hβ2 are quantified by high-resolution solution NMR. The trans conformer is most preferred in the D-β-Asp side-chain, whereas gauche+ and gauche- are abundant in L-α- and D-α-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 α- to β-Asp. The cyclization is not allowed in the trans conformer because of the long distance between CCOO- and N, to keep D-β-Asp stable. The change from gauche to trans conformer in D-β-Asp is exothermic and enthalpy-driven.
authors.affiliation: Faculty of Pharmaceutical Sciences Himeji Dokkyo University, 7-2-1 Kamiohno, Himeji 670-8524, Japan.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Aki
authors.affiliation: Faculty of Pharmaceutical Sciences Himeji Dokkyo University, 7-2-1 Kamiohno, Himeji 670-8524, Japan. Electronic address: emiko@himeji-du.ac.jp.
authors.forename: Emiko
authors.initials: E
authors.lastname: Okamura
mesh_terms: D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000737:chemistry*; D003500:Cyclization; D006801:Humans; D007908:Lens, Crystalline / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D011789:Quantum Theory; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D010455:Peptides; D001224:Aspartic Acid
keywords: Aspartate isomer; High-resolution solution NMR; Side-chain conformation; Spin–spin coupling constant; αA-Crystallin