Am. J. Respir. Crit. Care Med., Volume 165, Number 3, February 2002, 391-397

Cockroach Allergen Bla g 2 
Structure, Function, and Implications for Allergic Sensitization

ANNA POMÉS, MARTIN D. CHAPMAN, LISA D. VAILES, TOM L. BLUNDELL, and VENUGOPAL DHANARAJ

Asthma and Allergic Diseases Center, Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia; and Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom

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.

This article has been cited by other articles:

				Y. W. Tan, S. L. Chan, T. C. Ong, L. Y. Yit, Y. S. Tiong, F. T. Chew, J. Sivaraman, and Y. K. Mok Structures of Two Major Allergens, Bla g 4 and Per a 4, from Cockroaches and Their IgE Binding Epitopes J. Biol. Chem., January 30, 2009; 284(5): 3148 - 3157. [Abstract] [Full Text] [PDF]

				M. Li, A. Gustchina, J. Alexandratos, A. Wlodawer, S. Wunschmann, C. L. Kepley, M. D. Chapman, and A. Pomes Crystal Structure of a Dimerized Cockroach Allergen Bla g 2 Complexed with a Monoclonal Antibody J. Biol. Chem., August 15, 2008; 283(33): 22806 - 22814. [Abstract] [Full Text] [PDF]

				K. Y. Jeong, H. Hwang, J. Lee, I.-Y. Lee, D. S. Kim, C.-S. Hong, H.-I. Ree, and T.-S. Yong Allergenic Characterization of Tropomyosin from the Dusky Brown Cockroach, Periplaneta fuliginosa Clin. Vaccine Immunol., July 1, 2004; 11(4): 680 - 685. [Abstract] [Full Text] [PDF]

				M. J. Tobin Asthma, Airway Biology, and Nasal Disorders in AJRCCM 2002 Am. J. Respir. Crit. Care Med., February 1, 2003; 167(3): 319 - 332. [Full Text] [PDF]