Characterization of dynorphin A-converting enzyme in human spinal cord. An endoprotease related to a distinct conversion pathway for the opioid heptadecapeptide?
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.
Silberring
J
J
Department of Pharmacology, University of Uppsala, Sweden.
Castello
M E
ME
Nyberg
F
F
D000595:Amino Acid Sequence; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003546:Cysteine Endopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D004399:Dynorphins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004745:Enkephalins / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000378:metabolism; D013116:Spinal Cord / Q000201:enzymology*; D013379:Substrate Specificity
D004745:Enkephalins; D010446:Peptide Fragments; D017465:Receptors, Opioid, delta; D004399:Dynorphins; D003546:Cysteine Endopeptidases; C077484:dynorphin A-converting enzyme