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The potential role of α 2 ‐macroglobulin in the control of cysteine proteinases (gingipains) from Porphyromonas gingivalis
Author(s) -
Gron H.,
Pike R.,
Potempa J.,
Travis J.,
Thøgersen I. B.,
Enghild J. J.,
Pizzo' S. V.
Publication year - 1997
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.1600-0765.1997.tb01383.x
Subject(s) - porphyromonas gingivalis , macroglobulin , biochemistry , cysteine , enzyme , chemistry , cysteine proteinase inhibitors , cysteine protease , proteases , microbiology and biotechnology , biology , bacteria , genetics , programmed cell death , caspase , apoptosis
Porphyromonas gingivalis is closely associated with the development of some forms of periodontitis. The major cysteine proteinases released by this bacterium hydrolyze peptide bonds only after arginyl (gingipain R) or lysyl residues (gingipain K). No target protein inhibitors have been identified for either enzyme, leading us to investigate their inhibition by human plasma α 2 ‐macroglobulin (α 2 M). Both 50‐ and 95 kDa gingipain R were efficiently inhibited by α 2 M, whereas the catalytic activity of gingipain K could not be eliminated. All 3 enzymes were, however, inhibited by a homologous macroglobulin from rat plasma, α 1 ‐inhibitor‐3 a‐Macroglobulins must be cleaved in the so‐called “bait region“ in order to inhibit proteinases by a mechanism involving physical entrapment of the enzyme. A comparison of the aminio acid sequences of the 2 macroglobulins indicates that the lack of lysyl residues within the bait region of α 2 M protects Lys‐specific proteinases from being trapped. On this basis, other highly specific proteinases might also not be inhibited by α 2 M, possibly explaining the inability of the inhibitor to control proteolytic activity in some bacterially induced inflammatory states, despite its abundance (2‐5 mg/ml) in vascular fluids.