title: Cockroach allergen Bla g 2: structure, function, and implications for allergic sensitization.
abstract: Exposure to German cockroach (Blattella germanica) allergens is associated with the development of chronic respiratory diseases, especially asthma. The mechanism by which allergic patients develop specific immunoglobulin E (IgE) responses to environmental allergens is unknown. However, recent reports provided evidence that enzyme activity, especially proteolytic activity, was a major contributor to allergenicity. Bla g 2 is one of the most potent cockroach allergens (prevalence of IgE responses of 60 to 80%) and shows homology to the aspartic proteinase family of enzymes. We investigated whether the allergenicity of Bla g 2 was linked to its putative enzymatic function. A molecular model of Bla g 2, based on the high resolution crystal structures of pepsin and chymosin, showed that the overall three-dimensional structure of Bla g 2 was similar to that of aspartic proteinases with a well-defined binding pocket. However, critical amino acid substitutions in the catalytic triads and in the "flap" region of the molecule suggested that Bla g 2 was inactive and homologous to mammalian pregnancy-associated glycoproteins. This was confirmed experimentally by enzyme assay. The results show dissociation between enzymatic activity and allergenicity for Bla g 2 and suggest that other genetic and environmental factors are important determinants of sensitization.
authors.affiliation: Asthma and Allergic Diseases Center, Department of Internal Medicine, University of Virginia Health System, Charlottesville, VA, 22903, USA. apomes@inbio.com
authors.forename: Anna
authors.initials: A
authors.lastname: Pomés
authors.forename: Martin D
authors.initials: MD
authors.lastname: Chapman
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Vailes
authors.forename: Tom L
authors.initials: TL
authors.lastname: Blundell
authors.forename: Venugopal
authors.initials: V
authors.lastname: Dhanaraj
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000276:immunology*; D003058:Cockroaches / Q000276:immunology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D012130:Respiratory Hypersensitivity / Q000276:immunology*
chemical_list: D016282:Aspartic Acid Endopeptidases; C094699:allergen Bla g 2