Interaction of bovine serum amine oxidase with the polyamine oxidase inactivator MDL 72527.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0006-291X (Print) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
    • Publication Information:
      Publication: <2002- >: San Diego, CA : Elsevier
      Original Publication: New York, Academic Press.
    • Subject Terms:
      Amine Oxidase (Copper-Containing)/*blood ; Oxidoreductases Acting on CH-NH Group Donors/*antagonists & inhibitors ; Putrescine/*analogs & derivatives; Amine Oxidase (Copper-Containing)/chemistry ; Animals ; Benzoquinones/chemistry ; Cattle ; Enzyme Inhibitors/pharmacology ; Kinetics ; Models, Chemical ; Molecular Conformation ; Phenethylamines/chemistry ; Phenylhydrazines/chemistry ; Protein Binding ; Putrescine/pharmacology ; Spectrophotometry ; Temperature ; Time Factors ; Polyamine Oxidase
    • Abstract:
      MDL 72527 was considered a selective inhibitor of FAD-dependent polyamine oxidases. In the present communication, we demonstrate that MDL 72527 inactivates bovine serum amine oxidase, a copper-containing, TPQ-enzyme, time-dependently at 25 degrees C. In striking contrast, the enzyme remained active after incubation with excessive MDL 72527 at 37 degrees C, even after 70 h of incubation. Inactivation of BSAO with MDL 72527 at 25 degrees C did not involve the cofactor, as was shown by spectroscopy and by reaction with phenylhydrazine. Docking of MDL 72527 is difficult, owing to its size and two lipophilic moieties, and it has been shown that minor changes in reaction rate of substrates cause major changes in K(m) and k(cat)/K(m). We hypothesise that subtle conformational changes between 25 and 37 degrees C impair MDL 72527 from productive binding and prevent the nucleophilic group from reacting with the double bond system.
    • Accession Number:
      0 (Benzoquinones)
      0 (Enzyme Inhibitors)
      0 (Phenethylamines)
      0 (Phenylhydrazines)
      064F424C9K (phenylhydrazine)
      1YVR349GN4 (MDL 72527)
      3T006GV98U (quinone)
      41241-46-7 (2,3,5-trihydroxyphenethylamine)
      EC 1.4.3.21 (Amine Oxidase (Copper-Containing))
      EC 1.5.- (Oxidoreductases Acting on CH-NH Group Donors)
      V10TVZ52E4 (Putrescine)
    • Publication Date:
      Date Created: 20051229 Date Completed: 20060406 Latest Revision: 20231213
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.bbrc.2005.12.066
    • Accession Number:
      16380084