Glutaminyl cyclases display significant catalytic proficiency for glutamyl substrates

Biochemistry
Franziska SeifertStephan Schilling

Abstract

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.

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Citations

Jun 19, 2013·Insect Biochemistry and Molecular Biology·Steven W AdamsonShahid Karim
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May 13, 2014·Toxicon : Official Journal of the International Society on Toxinology·Ying-Ming WangInn-Ho Tsai
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Apr 7, 2021·Biological Chemistry·Sebastiaan LamersDavid Ruiz-Carrillo
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Jul 8, 2021·Molecular Pharmaceutics·Lia M BersinElizabeth M Topp
Jul 27, 2021·Acta Neuropathologica·Maike Hartlage-RübsamenSteffen Roßner

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