title: Succinimidyl residue formation in hen egg-white lysozyme favors the formation of intermolecular covalent bonds without affecting its tertiary structure.
abstract: Protein chemical degradations occur naturally into living cells as soon as proteins have been synthesized. Among these modifications, deamidation of asparagine or glutamine residues has been extensively studied, whereas the intermediate state, a succinimide derivative, was poorly investigated because of the difficulty of isolating those transient species. We used an indirect method, a limited thermal treatment in the dry state at acidic pH, to produce stable cyclic imide residues in hen lysozyme molecules, enabling us to examine the structural and functional properties of so modified proteins. Five cyclic imide rings have been located at sites directly accessible to solvent and did not lead to any changes in secondary or tertiary structures. However, they altered the catalytic properties of lysozyme and significantly decreased the intrinsic stability of the molecules. Moreover, dimerization occurred during the treatment, and this phenomenon was proportional to the extent of chemical degradation. We propose that succinimide formation could be responsible for covalent bond formation under specific physicochemical conditions that could be found in vivo.
authors.affiliation: Agrocampus Ouest and INRA, UMR1253 STLO, F-35042 Rennes, France. yann.desfougeres@unil.ch
authors.forename: Yann
authors.initials: Y
authors.lastname: Desfougères
authors.forename: Julien
authors.initials: J
authors.lastname: Jardin
authors.forename: Valérie
authors.initials: V
authors.lastname: Lechevalier
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pezennec
authors.forename: Françoise
authors.initials: F
authors.lastname: Nau
mesh_terms: D000818:Animals; D002384:Catalysis; D002645:Chickens; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D009113:Muramidase / Q000737:chemistry*; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D013388:Succinimides / Q000737:chemistry*; D013552:Swine
chemical_list: D013388:Succinimides; C032620:succinimide; D009113:Muramidase