A novel soluble protein factor with non-opioid dynorphin A-binding activity

Zoya Marinova, Tatjana Yakovleva, Matthias F. Melzig, Mathias Hallberg, Ingrid Nylander, Kallol Ray, David W. Rodgers, Kurt F. Hauser, Tomas J. Ekström, Georgy Bakalkin

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

A novel soluble non-opioid dynorphin A-binding factor (DABF) was identified and characterized in neuronal cell lines, rat spinal cord, and brain. DABF binds dynorphin A(1-17), dynorphin A(2-17), and the 32 amino acid prodynorphin fragment big dynorphin consisting of dynorphin A and B, but not other opioid and non-opioid peptides, opiates, and benzomorphans. The IC 50 for dynorphin A(1-17), dynorphin A(2-17), and big dynorphin is in the 5-10nM range. Using dynorphin A and big dynorphin fragments a binding epitope was mapped to dynorphin A(6-13). DABF has a molecular mass of about 70kDa. SH-groups are apparently involved in the binding of dynorphin A since p-hydroxy-mercuribenzoic acid inhibited this process. Upon interaction with DABF dynorphin A was converted into Leu-enkephalin, which remained bound to the protein. These data suggest that DABF functions as an oligopeptidase that forms stable and specific complexes with dynorphin A. The presence of DABF in brain structures and other tissues with low level of prodynorphin expression suggests that DABF as an oligopeptidase may degrade other peptides. Dynorphin A at the sites of its release in the CNS may attenuate this degradation as a competitor when it specifically binds to the enzyme.

Original languageEnglish
Pages (from-to)202-209
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume321
Issue number1
DOIs
StatePublished - Aug 13 2004

Bibliographical note

Funding Information:
We thank Mrs. Karin Hjertman for participation in initial experiments. This work was supported by grants from the Swedish Science Council to G.B. and the Swedish AFA Foundation to G.B. and T.J.E.

Keywords

  • Binding site
  • Conversion
  • Dynorphin
  • Non-opioid effects
  • Oligopeptidase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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