Identification of bikunin as an endogenous inhibitor of dynorphin convertase in human cerebrospinal fluid.
Dynorphin-converting enzymes constitute a group of peptidases capable of converting dynorphins to enkephalins. Through the action of these enzymes, the dynorphin-related peptides bind to delta-opioid instead of kappa-opioid receptors, leading to a change in the biological function of the neuropeptides. In this article, we describe the identification of the protein bikunin as an endogenous, competitive inhibitor of a dynorphin-converting enzyme in human cerebrospinal fluid. This protein is present together with its target enzyme in the same body fluids. The K(M) value of the convertase was found to be 9 microm, and the K(i) value of the inhibitor was 1.7 nm. The finding indicates that bikunin may play a significant role as a regulatory mechanism of neuropeptides, where one bioactive peptide is converted to a shorter sequence, which in turn, can affect the action of its longer form.
Suder
Piotr
P
Department of Neurobiochemistry, Faculty of Chemistry and Regional Laboratory, Jagiellonian University, Krakow, Poland.
Bierczynska-Krzysik
Anna
A
Kraj
Agnieszka
A
Brostedt
Peter
P
Mak
Pawel
P
Stawikowski
Maciej
M
Rolka
Krzysztof
K
Nyberg
Fred
F
Fries
Erik
E
Silberring
Jerzy
J
D000510:Alpha-Globulins / Q000134:cerebrospinal fluid* / Q000302:isolation & purification / Q000502:physiology*; D000595:Amino Acid Sequence; D002556:Cerebrospinal Fluid Proteins / Q000302:isolation & purification / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000134:cerebrospinal fluid*; D015853:Cysteine Proteinase Inhibitors / Q000134:cerebrospinal fluid / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data
D000510:Alpha-Globulins; D002556:Cerebrospinal Fluid Proteins; D015853:Cysteine Proteinase Inhibitors; C016001:alpha-1-microglobulin; D003546:Cysteine Endopeptidases; C063078:dynorphin converting enzyme