PMID- 11818327 OWN - NLM STAT- MEDLINE DCOM- 20020401 LR - 20091119 IS - 1073-449X (Print) IS - 1073-449X (Linking) VI - 165 IP - 3 DP - 2002 Feb 1 TI - Cockroach allergen Bla g 2: structure, function, and implications for allergic sensitization. PG - 391-7 AB - 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. FAU - Pomes, Anna AU - Pomes A AD - Asthma and Allergic Diseases Center, Department of Internal Medicine, University of Virginia Health System, Charlottesville, VA, 22903, USA. apomes@inbio.com FAU - Chapman, Martin D AU - Chapman MD FAU - Vailes, Lisa D AU - Vailes LD FAU - Blundell, Tom L AU - Blundell TL FAU - Dhanaraj, Venugopal AU - Dhanaraj V LA - eng SI - GENBANK/AF220040 GR - AI 32557/AI/NIAID NIH HHS/United States GR - AI 34601/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Respir Crit Care Med JT - American journal of respiratory and critical care medicine JID - 9421642 RN - EC 3.4.23.- (Aspartic Acid Endopeptidases) RN - EC 3.4.23.- (allergen Bla g 2) SB - IM MH - Amino Acid Sequence MH - Animals MH - Aspartic Acid Endopeptidases/*immunology MH - Cockroaches/*immunology MH - Models, Molecular MH - Molecular Sequence Data MH - Protein Structure, Quaternary MH - Respiratory Hypersensitivity/*immunology EDAT- 2002/01/31 10:00 MHDA- 2002/04/02 10:01 CRDT- 2002/01/31 10:00 PHST- 2002/01/31 10:00 [pubmed] PHST- 2002/04/02 10:01 [medline] PHST- 2002/01/31 10:00 [entrez] AID - 10.1164/ajrccm.165.3.2104027 [doi] PST - ppublish SO - Am J Respir Crit Care Med. 2002 Feb 1;165(3):391-7. doi: 10.1164/ajrccm.165.3.2104027.