A MBP-FAAH fusion protein as a tool to produce human and rat fatty acid amide hydrolase: Expression and pharmacological comparison

Geoffray Labar, F. V. Vliet, Johan Wouters, D. M. Lambert

Research output: Contribution to journalArticle

Abstract

Fatty acid amide hydrolase (FAAH), a membrane-anchored enzyme responsible for the termination of endocannabinoid signalling, is an attractive target for treating conditions such as pain and anxiety. Inhibitors of the enzyme, optimized using rodent FAAH, are known but their pharmacology and medicinal chemistry properties on the human FAAH are missing. Therefore recombinant human enzyme would represent a powerful tool to evaluate new drug candidates. However, the production of high amounts of enzyme is hampered by the known refractiveness of FAAH to overexpression. Here, we report the successful overexpression of rat and human FAAH as a fusion to the E. coli maltose-binding protein, retaining catalytic properties of native FAAH. Several known FAAH inhibitors were tested and differences in their potencies toward the human and rat FAAH were found, underscoring the importance of using a human FAAH in the development of inhibitors.

Original languageEnglish
Pages (from-to)127-133
Number of pages7
JournalAmino acids
Volume34
Issue number1
DOIs
Publication statusPublished - 1 Jan 2008

Keywords

  • Endocannabinoid system
  • Fatty acid amide hydrolase
  • Fusion proteins
  • Inhibitors characterization
  • Maltose-binding protein
  • Protein overexpression

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