HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Proteolytic activation of human pancreatitis-associated protein is required for peptidoglycan binding and bacterial aggregation.

Abstract
PAP (pancreatitis-associated protein) is a 16 kDa lectin-like protein, which becomes robustly up-regulated in the pancreatic juice during acute pancreatitis. Trypsin cleaves the N-terminus of PAP, which in turn forms insoluble fibrils. PAP and its paralogue, the pancreatic stone protein, induce bacterial aggregation and, more recently, PAP was shown to bind to the peptidoglycan of Gram-positive bacteria and exert a direct bactericidal effect. However, the role of N-terminal processing in the antibacterial function of PAP has remained unclear. In the present study, we demonstrate that N-terminal cleavage of PAP by trypsin at the Arg37-Ile38 peptide bond or by elastase at the Ser35-Ala36 peptide bond is a prerequisite for binding to the peptidoglycan of the Gram-positive bacterium Bacillus subtilis. The tryptic site in PAP was also efficiently cleaved by nprE (extracellular neutral metalloprotease) secreted from B. subtilis. Trypsin-mediated processing of PAP resulted in the formation of the characteristic insoluble PAP species, whereas elastase-processed PAP remained soluble. N-terminally processed PAP induced rapid aggregation of B. subtilis without significant bacterial killing. The bacteria-aggregating activities of trypsin-processed and elastase-processed PAP were comparable. In contrast with previous reports, the Gram-negative Escherichia coli bacterium was not aggregated. We conclude that N-terminal processing is necessary for the peptidoglycan binding and bacteria-aggregating activity of PAP and that trypsin-processed and elastase-processed forms are functionally equivalent. The observations also extend the complement of proteases capable of PAP processing, which now includes trypsins, pancreatic elastases and bacterial zinc metalloproteases of the thermolysin type.
AuthorsPéter Medveczky, Richárd Szmola, Miklós Sahin-Tóth
JournalThe Biochemical journal (Biochem J) Vol. 420 Issue 2 Pg. 335-43 (May 13 2009) ISSN: 1470-8728 [Electronic] England
PMID19254208 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Lectins, C-Type
  • Pancreatitis-Associated Proteins
  • Peptidoglycan
  • REG3A protein, human
  • Metalloproteases
  • Pancreatic Elastase
  • Trypsin
Topics
  • Amino Acid Sequence
  • Antigens, Neoplasm (genetics, metabolism)
  • Bacillus subtilis (chemistry, enzymology, physiology)
  • Bacterial Adhesion
  • Biomarkers, Tumor (genetics, metabolism)
  • Humans
  • Lectins, C-Type (genetics, metabolism)
  • Metalloproteases (metabolism)
  • Microbial Viability
  • Molecular Sequence Data
  • Pancreatic Elastase (metabolism)
  • Pancreatitis-Associated Proteins
  • Peptidoglycan (metabolism)
  • Protein Binding
  • Protein Processing, Post-Translational
  • Sequence Homology, Amino Acid
  • Trypsin (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: