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Pancreatic secretory trypsin inhibitor acts as an effective inhibitor of cysteine proteinases gingipains from Porphyromonas gingivalis
Author(s) -
Bania J.,
Kubiak A.,
Wojtachnio K.,
Polanowski A.
Publication year - 2008
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.2007.01020.x
Subject(s) - porphyromonas gingivalis , cysteine , trypsin , trypsin inhibitor , chemistry , biochemistry , enzyme , periodontal pathogen , microbiology and biotechnology , biology , periodontitis , medicine
Background and Objective: Porphyromonas gingivalis has been implicated as the major pathogen of periodontitis in adults. This organism produces an array of virulence factors, of which cysteine proteinases, referred to as gingipains K and R, are believed to play a crucial role in pathogenicity. The aim of this study was to investigate the susceptibility of gingipains K and R to inhibition by a pancreatic secretory trypsin inhibitor. Material and Methods: Enzyme activities were measured spectrophotometrically using chromogenic turnover substrates. To estimate the value of the association constant ( K a ), constant amounts of enzyme were reacted with increasing amounts of inhibitor to reach equilibrium. The K a was calculated by fitting the experimental data to the given equation. Results: In this study it was shown that gingipains are susceptible to pancreatic Kazal‐type trypsin inhibitors (pancreatic secretory trypsin inhibitors). Bovine pancreatic secretory trypsin inhibitor, having an Arg residue at the P 1 position of the reactive site, specifically inhibited the activity of the Arg‐specific cysteine proteinase gingipain R, whereas porcine inhibitor, possessing a Lys residue at the P 1 position, exhibited activity only against the Lys‐specific cysteine proteinase gingipain K. The K a values for the inhibitor–proteinase interaction were 1.6 × 10 6 m −1 and 2.0 × 10 4 m −1 for gingipain R and gingipain K, respectively. Conclusion: This finding is the first demonstration of the inhibitory potency of the Kazal‐type specific trypsin inhibitors against cysteine proteinases. These discoveries open new possibilities for the use of naturally occurring inhibitors, displaying activity across enzyme families, as a model in designing new molecules of therapeutic significance.