title: Analysis of the specificity of bacterial immunoglobulin A (IgA) proteases by a comparative study of ape serum IgAs as substrates.
abstract: Immunoglobulin A (IgA) proteases are bacterial enzymes with substrate specificity for human serum and secretory IgAs. To further define the basis of this specificity, we examined the ability of IgA proteases of Clostridium ramosum, Streptococcus pneumoniae (EC 3.4.24.13), Neisseria meningitidis (EC 3.4.21.72), and Haemophilus influenzae (EC 3.4.21.72) to cleave serum IgAs of gorillas, chimpanzees, and orangutans. All enzymes cleaved the IgAs of the three apes despite differences in ape IgA1 hinge sequence relative to the human prototype. To directly compare the ape and human hinge cleavage sites, the sites were identified in eight ape IgA digests. This analysis confirmed that ape proteins were all cleaved in the IgA hinge region, in all but one case after proline residues. The exception, C. ramosum protease, cleaved gorilla and chimpanzee IgAs at peptide bonds having no proline, but the scissile bonds were in the same hinge location as the Pro-221-Val-222 cleaved in human IgA1. These data indicate that proline is not an invariant substrate requirement for all IgA proteases and that the location of the scissile bond, in addition to its composition, is a critical determinant of cleavage specificity.
authors.affiliation: Gastroenterology Division, Department of Medicine, Tufts-New England Medical Center, Boston, Massachusetts 02111, USA.
authors.forename: J
authors.initials: J
authors.lastname: Qiu
authors.forename: G P
authors.initials: GP
authors.lastname: Brackee
authors.forename: A G
authors.initials: AG
authors.lastname: Plaut
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000201:enzymology*; D006071:Gorilla gorilla; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D011148:Pongo pygmaeus; D012697:Serine Endopeptidases / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D007070:Immunoglobulin A; D012697:Serine Endopeptidases; C021433:IgA-specific serine endopeptidase