Studies of specificity and inhibition of human cerebrospinal fluid dynorphin converting enzyme.
Dynorphin-converting activity was recently discovered in human cerebrospinal fluid. This enzyme (hCSF-DCE) cleaves dynorphin A, dynorphin B and alpha-neoendorphin to release Leu-enkephalin-Arg6. To characterize the enzyme further we used several protease inhibitors, including N-peptidyl-O-acyl hydroxylamines which are known to act as potent irreversible inhibitors of serine and cysteine proteinases. No irreversible inactivation occurred but strong, reversible effects on the dynorphin-converting activity by some of the inhibitors tested could be observed. Although, hCSF-DCE binds its substrates (dynorphin A and B) in the microM-mM concentration range, it exhibits high specificity in recognizing and cleaving the linkage between the two basic amino acids in the substrate sequence.
Department of Biotechnology, Martin-Luther-University of Halle, Saale, East Germany.
H U
HU
Demuth
F
F
Nyberg
D000595:Amino Acid Sequence; D003546:Cysteine Endopeptidases / Q000134:cerebrospinal fluid / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000031:analogs & derivatives / Q000378:metabolism; D004723:Endorphins / Q000378:metabolism; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000096:biosynthesis; D006801:Humans; D006898:Hydroxylamines / Q000494:pharmacology; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D013379:Substrate Specificity
D004723:Endorphins; D006898:Hydroxylamines; D010455:Peptides; D011480:Protease Inhibitors; D004743:Enkephalin, Leucine; D004399:Dynorphins; C026768:enkephalin-Leu, Arg(6)-; C036200:rimorphin; D003546:Cysteine Endopeptidases; C063078:dynorphin converting enzyme