Characterization of dynorphin A-converting enzyme in human spinal cord. An endoprotease related to a distinct conversion pathway for the opioid heptadecapeptide?

• Published in: The Journal of biological chemistry 1992-10, Vol.267 (30), p.21324-21328
• Main Authors: Silberring, J, Castello, M.E., Nyberg, F
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; characterization; Chromatography, Gel; Chromatography, High Pressure Liquid; Cysteine Endopeptidases - isolation & purification; Cysteine Endopeptidases - metabolism; dynorphin A-converting enzyme; Dynorphins - metabolism; Electrophoresis, Polyacrylamide Gel; endopeptidase; Enkephalins - metabolism; Humans; man; Molecular Sequence Data; Peptide Fragments - metabolism; Receptors, Opioid, delta - metabolism; spinal cord; Spinal Cord - enzymology; Substrate Specificity
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)36612-8

A highly specific proteinase, converting dynorphin A (1-17) to enkephalins, was isolated from the human spinal cord and subjected to further characterization. The enzyme was found to be a thiol-dependent protein with a relative molecular mass of 50 kDa and a pH optimum between 5.0 and 5.5. This proteinase appears to exclusively convert dynorphin A (1-17) to Leu-enkephalin and its COOH-terminal extensions Leu-enkephalin-Arg6 (which was a major conversion product) and Leu-enkephalin-Arg6-Arg7 but not the other prodynorphin- or proenkephalin-derived peptides. This high specificity toward a single structure is suggested to be involved in a distinct processing pathway associated with the generation of the opioid peptides with selectivity for delta-opioid receptors.