Glutaminyl Cyclases Display Significant Catalytic Proficiency for Glutamyl Substrates

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• 作者：Franziska Seifert ; Katrin Schulz ; Birgit Koch ; Susanne Manhart ; Hans-Ulrich Demuth ; Stephan Schilling
• 刊名：Biochemistry
• 出版年：2009
• 出版时间：December 22, 2009
• 年：2009
• 卷：48
• 期：50
• 页码：11831-11833
• 全文大小：698K
• 年卷期：v.48,no.50(December 22, 2009)
• ISSN：1520-4995

文摘

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 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 × 10⁵ 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.