title: Inhibitory effect of alpha 2-macroglobulin on Vibrio vulnificus protease.
abstract: Vibrio vulnificus, an etiologic agent of wound infections and septicemia in humans, elaborates a metalloprotease which is known to be an important virulence factor of the Vibrio. The proteolytic activity of V. vulnificus metalloprotease (VVP) toward casein and elastin was inhibited by alpha 2-macroglobulin (alpha 2 M) at the molar ratio of 1:1, although partial activity was maintained. Permeability-enhancing and hemorrhagic activities were also inhibited, but the peptidase activity toward Z-Gly-Phe-NH2 was not reduced, even by an excess amount of alpha 2 M. VVP formed a complex with alpha 2 M through cleavage of the bait regions of all four alpha 2 M subunits and elicitation of conformational change of the alpha 2 M molecule, which resulted in entrapment of VVP in the alpha 2 M molecule. The peptidase activity of alpha 2 M-VVP complex was inhibited by low-molecular-weight inhibitors such as phosphoramidon, but IgG antibody against VVP failed to neutralize its peptidase activity. Of human plasma proteins, alpha 2 M was the only inhibitor for VVP. These findings indicate that VVP produced during V. vulnificus infection is inactivated by plasma alpha 2 M that leaks from the vascular system.
authors: Faculty of Pharmaceutical Sciences, Okayama University.
authors: S
authors: S
authors: Miyoshi
authors: S
authors: S
authors: Shinoda
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000032:analysis; D002364:Caseins / Q000378:metabolism; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D006470:Hemorrhage / Q000139:chemically induced; D010447:Peptide Hydrolases / Q000032:analysis / Q000494:pharmacology / Q000633:toxicity; D011480:Protease Inhibitors; D051381:Rats; D012822:Silicon Dioxide; D014733:Vibrio / Q000201:enzymology*; D000511:alpha-Macroglobulins / Q000032:analysis / Q000494:pharmacology*
chemical_list: D001798:Blood Proteins; D002364:Caseins; D011480:Protease Inhibitors; D000511:alpha-Macroglobulins; D012822:Silicon Dioxide; C049272:Spherogel TSK 2000SW; D010447:Peptide Hydrolases