Article citationsMore>>

Kuge, K., Fujii, N., Miura, Y., Tajima, S. and Saito, T. (2004) Kinetic study of racemization of aspartyl residues in synthetic elastin peptides. Amino Acids, 27, 193-197.
http://dx.doi.org/10.1007/s00726-004-0107-3

has been cited by the following article:

• TITLE: Two-water-assisted racemization of the succinimide intermediate formed in proteins. A computational model study

  AUTHORS: Ohgi Takahashi

  KEYWORDS: Aspartic Acid Residue; Racemization; Nonenzymatic Reaction; Succinimide; Water Catalysis; Enolization; Computational Chemistry; Density Functional Theory

  JOURNAL NAME: Health, Vol.5 No.12, December 18, 2013

  ABSTRACT: Racemization of aspartic acid (Asp) residues in proteins plays an important role in the molecular biology of aging. In the widely accepted mechanism of the Asp racemization, a succinimide (SI) intermediate is the species which actually undergo the direct racemization. In the present study, a two-water-assisted mechanism of the SI racemization was computationally investigated using a model compound in which an aminosuccinyl (Asu) residue is capped with acetyl and NMe groups on the N-and C-termini, respectively. The two water molecules catalyze the enolization of the Hα-Cα-C=O portion in the Asu residue by mediating proton relay from the α-carbon atom to the carboxyl oxygen atom. After the enolization, migration of the water molecules and conformational change lead to the mirror image of the initially formed enol two-water complex, and the racemization is completed by the following ketonization. The overall activation barrier (28.2 kcal·mol-1) corresponds to the enolization and ketonization steps, and falls within the available experimental activation energies (21.4-29.0 kcal·mol-1). Therefore, the two-water-assisted mechanism investigated here is plausible for the in vivo and in vitro racemization reactions of the SI intermediates formed in peptides and proteins.