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Propeptide-Mediated Inhibition of Cognate Gingipain Proteinases

Abstract : Porphyromonas gingivalis is a major pathogen associated with chronic periodontitis. The organism’s cell-surface cysteine proteinases, the Arg-specific proteinases (RgpA, RgpB) and the Lys-specific proteinase (Kgp), which are known as gingipains have been implicated as major virulence factors. All three gingipain precursors contain a propeptide of around 200 amino acids in length that is removed during maturation. The aim of this study was to characterize the inhibitory potential of the Kgp and RgpB propeptides against the mature cognate enzymes. Mature Kgp was obtained from P. gingivalis mutant ECR368, which produces a recombinant Kgp with an ABM1 motif deleted from the catalytic domain (rKgp) that enables the otherwise membrane bound enzyme to dissociate from adhesins and be released. Mature RgpB was obtained from P. gingivalis HG66. Recombinant propeptides of Kgp and RgpB were produced in Escherichia coli and purified using nickel-affinity chromatography. The Kgp and RgpB propeptides displayed non-competitive inhibition kinetics with Ki values of 2.04 µM and 12 nM, respectively. Both propeptides exhibited selectivity towards their cognate proteinase. The specificity of both propeptides was demonstrated by their inability to inhibit caspase-3, a closely related cysteine protease, and papain that also has a relatively long propeptide. Both propeptides at 100 mg/L caused a 50% reduction of P. gingivalis growth in a protein-based medium. In summary, this study demonstrates that gingipain propeptides are capable of inhibiting their mature cognate proteinases
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Contributor : Laurent Jonchère <>
Submitted on : Monday, August 31, 2015 - 4:17:59 PM
Last modification on : Thursday, January 14, 2021 - 11:26:37 AM

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N. Laila Huq, Christine A. Seers, Elena C. Y. Toh, Stuart G. Dashper, Nada Slakeski, et al.. Propeptide-Mediated Inhibition of Cognate Gingipain Proteinases. PLoS ONE, Public Library of Science, 2013, 8 (6), pp.e65447. ⟨10.1371/journal.pone.0065447⟩. ⟨hal-01188858⟩



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