title: A serpin from the gut bacterium Bifidobacterium longum inhibits eukaryotic elastase-like serine proteases.
abstract: Serpins form a large class of protease inhibitors involved in regulation of a wide spectrum of physiological processes. Recently identified prokaryotic members of this protein family may provide a key to the evolutionary origins of the unique serpin fold and the associated inhibitory mechanism. We performed a biochemical characterization of a serpin from Bifidobacterium longum, an anaerobic Gram-positive bacterium that naturally colonizes human gastrointestinal tract. The B. longum serpin was shown to efficiently inhibit eukaryotic elastase-like proteases with a stoichiometry of inhibition close to 1. Porcine pancreatic elastase and human neutrophil elastase were inhibited with the second order association constants of 4.7 x 10(4) m(-1) s(-1) and 2.1 x 10(4) m(-1) s(-1), respectively. The B. longum serpin is expected to be active in the gastrointestinal tract, because incubation of the purified recombinant serpin with mouse feces produces a stable covalent serpin-protease adduct readily detectable by SDS-PAGE. Bifidobacteria may encounter both pancreatic elastase and neutrophil elastase in their natural habitat and protection against exogenous proteolysis may play an important role in the interaction between these commensal bacteria and their host.
authors.affiliation: Nestlé Research Center, Vers-chez-les-Blanc, P. O. Box 44, CH-1000 Lausanne 26, Switzerland. Electronic address: dmitri_ivanov@hms.harvard.edu.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Ivanov
authors.affiliation: Nestlé Research Center, Vers-chez-les-Blanc, P. O. Box 44, CH-1000 Lausanne 26, Switzerland.
authors.forename: Celine
authors.initials: C
authors.lastname: Emonet
authors.affiliation: Nestlé Research Center, Vers-chez-les-Blanc, P. O. Box 44, CH-1000 Lausanne 26, Switzerland.
authors.forename: Francis
authors.initials: F
authors.lastname: Foata
authors.affiliation: Nestlé Research Center, Vers-chez-les-Blanc, P. O. Box 44, CH-1000 Lausanne 26, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Affolter
authors.affiliation: Nestlé Research Center, Vers-chez-les-Blanc, P. O. Box 44, CH-1000 Lausanne 26, Switzerland.
authors.forename: Michelle
authors.initials: M
authors.lastname: Delley
authors.affiliation: Nestlé Research Center, Vers-chez-les-Blanc, P. O. Box 44, CH-1000 Lausanne 26, Switzerland.
authors.forename: Makda
authors.initials: M
authors.lastname: Fisseha
authors.affiliation: Nestlé Research Center, Vers-chez-les-Blanc, P. O. Box 44, CH-1000 Lausanne 26, Switzerland.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Blum-Sperisen
authors.affiliation: Nestlé Research Center, Vers-chez-les-Blanc, P. O. Box 44, CH-1000 Lausanne 26, Switzerland.
authors.forename: Sunil
authors.initials: S
authors.lastname: Kochhar
authors.affiliation: Nestlé Research Center, Vers-chez-les-Blanc, P. O. Box 44, CH-1000 Lausanne 26, Switzerland. Electronic address: fabrizio.arigoni@rdls.nestle.com.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Arigoni
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001644:Bifidobacterium / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D005243:Feces; D041981:Gastrointestinal Tract / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D019272:Leukocyte Elastase / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D017386:Sequence Homology, Amino Acid; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D015843:Serpins / Q000737:chemistry*; D013552:Swine
chemical_list: D015842:Serine Proteinase Inhibitors; D015843:Serpins; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase