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Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid conditions
Author(s) -
Schilling Stephan,
Hoffmann Torsten,
Manhart Susanne,
Hoffmann Matthias,
Demuth Hans-Ulrich
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(04)00300-x
Subject(s) - neurotensin , chemistry , enzyme , neuropeptide , biochemistry , glutamate receptor , hormone , cyclase , receptor
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.