Denatured human alpha-defensin attenuates the bactericidal activity and the stability against enzymatic digestion

Biochem Biophys Res Commun. 2007 Jun 22;358(1):349-55. doi: 10.1016/j.bbrc.2007.04.132. Epub 2007 Apr 30.


alpha-Defensin is an antimicrobial peptide which plays an important role in innate immunity. Human defensin (HD)-5 is stored in the Paneth cells of the small intestine as a pro-form and is cleaved by trypsin, which is co-secreted from the Paneth cell granules. The mature HD-5 is protected from further digestion by the proteolysis enzyme. We generated both recombinant HD-5 and proHD-5, and the reduced form of each peptide in order to determine their physiological roles of the disulfide bonds. The reduced proHD-5 attenuated the bactericidal activity and the stability against the trypsin digestion. Human defensin was protected from the enzymatic degradation by disulfide bridges. We further purified the HD-5 with a disulfide variation in the small intestine of Crohn's disease patients. The HD-5 was sensitive to the trypsin treatment. These observations evidently predict that a defensin deficiency may be caused by a disulfide disorder in the disease.

MeSH terms

  • Amino Acid Sequence
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Crohn Disease / metabolism
  • Disulfides / metabolism
  • Humans
  • Ileum / metabolism
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / pharmacology
  • Protein Denaturation
  • Protein Precursors / chemistry
  • Protein Precursors / pharmacology
  • Protein Precursors / physiology
  • Protein Processing, Post-Translational
  • Salmonella typhimurium / drug effects
  • Trypsin / metabolism
  • alpha-Defensins / chemistry
  • alpha-Defensins / pharmacology
  • alpha-Defensins / physiology*


  • Anti-Bacterial Agents
  • Disulfides
  • Peptides
  • Protein Precursors
  • alpha-Defensins
  • Trypsin