Voorter C E, de Haard-Hoekman W A, van den Oetelaar P J, Bloemendal H, de Jong W W
Department of Biochemistry, University of Nijmegen, The Netherlands.
J Biol Chem. 1988 Dec 15;263(35):19020-3.
Cleavage of specific peptide bonds occurs with aging in the alpha A subunit of bovine alpha-crystallin. One of the breaks occurs at residue Asn-101. This same residue undergoes in vivo deamidation, isomerization, and racemization. Deamidation and isomerization are known to occur via succinimide ring formation of labile asparagine residues. Model studies on peptides have shown that imide formation can also lead to peptide bond cleavage (Geiger, T., and Clarke, S. (1987) J. Biol. Chem. 262, 785-794). In that case, both asparagine and aspartic acid amide would be expected as C termini of the truncated polypeptide, and this is indeed the case in the alpha A-(1-101)-chain. This thus represents a first example of nonenzymatic in vivo peptide bond cleavage in an aging protein through the formation of a succinimide intermediate. In addition, we found that in bovine lens no detectable conversion (through the action of protein-carboxyl methyltransferase) of isoaspartyl to normal aspartyl residues occurs in vivo after deamidation of Asn-101.
随着衰老，牛α-晶状体蛋白αA亚基中的特定肽键会发生断裂。其中一处断裂发生在第101位天冬酰胺残基处。该残基在体内会发生脱酰胺、异构化和消旋化。已知脱酰胺和异构化是通过不稳定天冬酰胺残基的琥珀酰亚胺环形成而发生的。对肽的模型研究表明，亚胺形成也可导致肽键断裂（盖革，T.，和克拉克，S.（1987年）《生物化学杂志》262卷，785 - 794页）。在这种情况下，截短多肽的C端预期会同时出现天冬酰胺和天冬氨酸酰胺，而在αA -（1 - 101）链中确实如此。因此，这代表了衰老蛋白质中通过形成琥珀酰亚胺中间体在体内发生非酶促肽键断裂的首个例子。此外，我们发现，在牛晶状体中，天冬酰胺-101脱酰胺后，体内未检测到（通过蛋白质羧基甲基转移酶的作用）异天冬氨酰向正常天冬氨酰残基的转化。
