Probiodrug AG, Weinbergweg 22, 06120 Halle, Germany.
Biochemistry. 2009 Dec 22;48(50):11831-3. doi: 10.1021/bi9018835.
N-Terminal glutaminyl and glutamyl residues of peptides and proteins tend to form pyroglutamic acid (pGlu) by intramolecular cylization. The rate constants for spontaneous cyclization of glutamine (10(-6) s(-1)) and glutamic acid (10(-9) s(-1)) in aqueous solution differ by approximately 3 orders of magnitude at pH 6.5. Glutaminyl cyclases (QCs) from plants and mammals accelerate pGlu formation. Human QC exhibits a rate enhancement of 2.2 x 10(5) for glutamate cyclization, approximately 2 orders of magnitude lower than that of the corresponding N-terminal glutaminyl reaction. Thus, glutaminyl cyclases are enzymes with only modest specificity for cyclization of their primary glutaminyl substrates and may provide a link between glutamate cyclization and pathophysiology.
肽和蛋白质的 N-末端谷氨酰基和谷氨酸基残基倾向于通过分子内环化形成焦谷氨酸(pGlu)。在 pH 值为 6.5 时,谷氨酰胺(10(-6) s(-1))和谷氨酸(10(-9) s(-1))在水溶液中自发环化的速率常数相差约 3 个数量级。来自植物和哺乳动物的谷氨酰基环化酶(QC)加速 pGlu 的形成。人类 QC 对谷氨酸环化的速率增强为 2.2 x 10(5),大约低 2 个数量级,低于相应的 N-末端谷氨酰基反应。因此,谷氨酰基环化酶是对其主要谷氨酰基底物环化具有适度特异性的酶,它们可能为谷氨酸环化和病理生理学之间提供了联系。