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Updated: Aug 25, 2026

Reconstitution of the Bacterial Glutamate Receptor Channel by Encapsulation of a Cell-Free Expression System
Published on: March 8, 2024
Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid conditions
Stephan Schilling1, Torsten Hoffmann, Susanne Manhart
1Probiodrug AG, Biocenter, Weinbergweg 22, 06120 Halle/Saale, Germany.
Abstract:
N-terminal pyroglutamate (pGlu) formation from glutaminyl precursors is a posttranslational event in the processing of bioactive neuropeptides such as thyrotropin-releasing hormone and neurotensin during their maturation in the secretory pathway. The reaction is facilitated by glutaminyl cyclase (QC), an enzyme highly abundant in mammalian brain. Here, we describe for the first time that human and papaya QC also catalyze N-terminal glutamate cyclization. Surprisingly, the enzymatic Glu(1) conversion is favored at pH 6.0 while Gln(1) conversion occurs with an optimum at pH 8.0. This unexpected finding might be of importance for deciphering the events leading to deposition of highly toxic pyroglutamyl peptides in amyloidotic diseases.
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