Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid conditions

FEBS Letters

Schilling, Stephan¹  Hoffmann, Torsten¹  Hoffmann, Matthias¹  Manhart, Susanne¹  Demuth, Hans-Ulrich¹ 

[1] Probiodrug AG, Biocenter, Weinbergweg 22, 06120 Halle/Saale, Germany

关键词: Amyloid precursor protein;    Alzheimer's disease;    Glutamine cyclotransferase;    Glutaminyl cyclase;    Glutamyl cyclase;    AD;    Alzheimer's disease;    APP;    amyloid precursor protein;    Aβ(3–11)a;    amyloid-β peptide 3–11 amide;    βNA;    2-naphthylamine;    DPIV;    dipeptidyl peptidase IV;    EC;    glutamyl cyclase;    GnRH;    gonadotropin-releasing hormone;    pGlu;    pyroglutamic acid;    QC;    glutaminyl cyclase;    TRH;    thyrotropin-releasing hormone;   

DOI  :  10.1016/S0014-5793(04)00300-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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 Glu¹ conversion is favored at pH 6.0 while Gln¹ 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.

【 授权许可】

Unknown