Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid conditions

被引：152

作者：

Schilling, S ^{[1
]}

Hoffmann, T ^{[1
]}

Manhart, S ^{[1
]}

Hoffmann, M ^{[1
]}

Demuth, HU ^{[1
]}

机构：

[1] Probiodrug AG, Bioctr, D-06120 Halle An Der Saale, Germany

来源：

FEBS LETTERS | 2004年 / 563卷 / 1-3期

关键词：

amyloid precursor protein; Alzheimer's disease; glutamine cyclotransferase; glutaminyl cyclase; glutamyl cyclase;

D O I：

10.1016/S0014-5793(04)00300-X

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

引用

页码：191 / 196

页数：6

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