PMID: 9165075Mar 1, 1997Paper

Titration and mapping of the active site of cysteine proteinases from Porphyromonas gingivalis (gingipains) using peptidyl chloromethanes

Biological Chemistry
J PotempaJ Travis

Abstract

Porphyromonas gingivalis is one of the major pathogens associated with periodontal disease and releases powerful cysteine proteinases known as the gingipains, which are key virulence factors for this organism. The three forms of gingipains, gingipain R1, gingipain R2 (gingipain Rs) and gingipain K, which cleave specifically after arginine (R) or lysine (K) residues, were characterized in terms of the kinetics of their interaction with a wide range of synthetic peptidyl chloromethane inhibitors and a peptidyl (acyloxy)methane. Chloromethane inhibitors were found to inhibit all the enzymes to varying degree dependent on the peptidyl components of the inhibitor. Thus, inhibitors containing a basic residue at P1 rapidly inactivated the gingipains and some specificity could be seen at the P2 site. The (acyloxy)methane inhibitor, Cbz-Phe-Lys-CH2OCO-2,4,6-Me3-Ph, was very specific in its rapid inhibition of gingipain K over the gingipains R. This inhibitor, together with the peptidyl chloromethanes, D-Phe-Pro-Arg-CH2Cl and D-Phe-Phe-Arg-CH2Cl, which reacted most rapidly with the Arg-specific proteinases, could be used to active site titrate purified forms of the enzymes and enzymes found in crude fractions such as intact P. gingivalis...Continue Reading

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Citations

Jan 6, 2012·Applied Microbiology and Biotechnology·Jerica Sabotič, Janko Kos
Jan 29, 2010·Zeitschrift für Rheumatologie·J DetertF Buttgereit
Sep 7, 1999·Molecular and Biochemical Parasitology·R E MortyT H Coetzer
Jul 6, 2001·The Biochemical Journal·S J SnipasG S Salvesen
Jul 20, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Bjarne VincentsMagnus Abrahamson
Apr 16, 2002·Infection and Immunity·Jannet KatzDaniel F Balkovetz
Feb 26, 2005·Infection and Immunity·Renata Mezyk-KopecJoanna Bereta
Nov 20, 2002·Biological Chemistry·André J NiestrojHans-Ulrich Demuth
Feb 21, 2003·Journal of Periodontology·Takahisa Imamura
May 30, 2009·Molecular Immunology·Anna M BlomKristian Riesbeck
Sep 13, 2015·Journal of Clinical Periodontology·Kåre BuhlinPirkko J Pussinen
Sep 23, 2008·International Journal of Antimicrobial Agents·Robert P Allaker, C W Ian Douglas
Nov 7, 2015·Microbial Pathogenesis·Hong Min NgEric C Reynolds
Jan 6, 2009·Oral Microbiology and Immunology·P G StathopoulouD F Kinane
Jan 3, 2013·Molecular Oral Microbiology·E FröhlichS Eick
Dec 19, 2009·Periodontology 2000·Rishi D PathiranaEric C Reynolds
Feb 11, 2015·Virulence·Robert P Allaker, C W Ian Douglas
Mar 28, 2006·The American Journal of Pathology·Marinella HolzhausenNathalie Vergnolle
Mar 12, 2015·Cellular Microbiology·Young-Jung JungBong-Kyu Choi
Jan 18, 2005·FEMS Microbiology Reviews·Teresa OlczakCaroline Attardo Genco
Mar 1, 2011·European Journal of Microbiology & Immunology·N Li, C A Collyer
Apr 26, 2012·FEMS Microbiology Letters·Nagihan Bostanci, Georgios N Belibasakis

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