Structural analysis of thimet oligopeptidase (EC 3.4.24.15) through surface mutation E107Q E111Q
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Swapping the substrate specificities of the neuropeptidases neurolysin and thimet oligopeptidase.
Thimet oligopeptidase (EC 3.4.24.15) and neurolysin (EC 3.4.24.16) are closely related zinc-dependent metallopeptidases that metabolize small bioactive peptides. They cleave many substrates at the same sites, but they recognize different positions on others, including neurotensin, a 13-residue peptide involved in modulation of dopaminergic circuits, pain perception, and thermoregulation. On the...
متن کاملThimet oligopeptidase: similarity to 'soluble angiotensin II-binding protein' and some corrections to the published amino acid sequence of the rat testis enzyme.
The deduced amino acid sequence of pig liver soluble angiotensin II-binding protein [Sugiura, Hagiwara and Hirose (1992) J. Biol. Chem. 267, 18067-18072] is similar over most of its length to that reported for rat testis thimet oligopeptidase (EC 3.4.24.15) by Pierotti, Dong, Glucksman, Orlowski and Roberts [(1990) (Biochemistry 29, 10323-10329]. We have found that homogeneous rat testis thimet...
متن کاملRegulation of cell-surface major histocompatibility complex class I expression by the endopeptidase EC3.4.24.15 (thimet oligopeptidase).
Endopeptidase EP24.15 (EC 3.4.24.15; thimet oligopeptidase), traditionally classified as a neuropeptide-processing enzyme, degrades well-known MHC I (major histocompatibility complex class I) peptides in cell extracts. In the present study, we determine the contribution of EP24.15 in vivo to the surface expression of MHC I on intact cells. CTLs (cytotoxic T-lymphocytes) recognize a vast array o...
متن کاملNuclear Thimet oligopeptidase is coexpressed with oestrogen receptor alpha in hypothalamic cells and regulated by oestradiol in female mice.
Thimet oligopeptidase (EC 3.4.24.15; also called EP24.15 and TOP; referred to here as TOP) is a neuropeptidase involved in the regulation of several physiological functions including reproduction. Among its substrates is gonadotrophin-releasing hormone (GnRH), an important hypothalamic hormone that regulates the synthesis and release of oestradiol and facilitates female sexual behaviour. Using ...
متن کاملInteraction with calmodulin is important for the secretion of thimet oligopeptidase following stimulation.
Thimet oligopeptidase (EC 3.4.24.15; EP24.15) was originally described as a neuropeptide-metabolizing enzyme, highly expressed in the brain, kidneys and neuroendocrine tissue. EP24.15 lacks a typical signal peptide sequence for entry into the secretory pathway and is secreted by cells via an unconventional and unknown mechanism. In this study, we identified a novel calcium-dependent interaction...
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