TY - JOUR
T1 - Regulators of the neuropeptide-degrading enzyme, EC 3.4.24.15 (thimet oligopeptidase), in cerebrospinal fluid
AU - Shrimpton, Corie N
AU - Wolfson, Adele J
AU - Smith, Alexander Ian
AU - Lew, Rebecca A
PY - 2003
Y1 - 2003
N2 - Endopeptidase EC 3.4.24.15 (EP 24.15; thimet oligopeptidase) is a soluble metalloendopeptidase implicated in the metabolism of a number of neuropeptides, including neurotensin, gonadotropin-releasing hormone, and opioid peptides. We have shown previously that thiol reducing agents, such as dithiothreitol, activate EP 24.15 by mediating the conversion of inactive multimeric forms to active monomers and that this conversion involves the disruption of intermolecular disulfide bonds involving cysteine residues 246, 248, and 253. We have identified two components of cerebrospinal fluid that activate recombinant EP 24.15, but have no effect on a thiol-independent cysteine mutant form of the enzyme. The low molecular weight (50 kDa) is sensitive to digestion with trypsin, suggesting it is proteinaceous in nature. These results suggest that EP 24.15 activity in the brain may be modulated by factors released into cerebrospinal fluid.
AB - Endopeptidase EC 3.4.24.15 (EP 24.15; thimet oligopeptidase) is a soluble metalloendopeptidase implicated in the metabolism of a number of neuropeptides, including neurotensin, gonadotropin-releasing hormone, and opioid peptides. We have shown previously that thiol reducing agents, such as dithiothreitol, activate EP 24.15 by mediating the conversion of inactive multimeric forms to active monomers and that this conversion involves the disruption of intermolecular disulfide bonds involving cysteine residues 246, 248, and 253. We have identified two components of cerebrospinal fluid that activate recombinant EP 24.15, but have no effect on a thiol-independent cysteine mutant form of the enzyme. The low molecular weight (50 kDa) is sensitive to digestion with trypsin, suggesting it is proteinaceous in nature. These results suggest that EP 24.15 activity in the brain may be modulated by factors released into cerebrospinal fluid.
UR - http://www3.interscience.wiley.com/cgi-bin/fulltext/106561280/PDFSTART
U2 - 10.1002/jnr.10698
DO - 10.1002/jnr.10698
M3 - Article
VL - 74
SP - 474
EP - 478
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
SN - 0360-4012
IS - 3
ER -