Affiliation:
1. Department of Medicine, Tufts-New England Medical Center Hospital, Boston, Massachusetts 02111.
Abstract
The amino acid sequence T-P-P-T-P-S-P-S is tandemly duplicated in the heavy chain of human immunoglobulin A1 (IgA1), the major antibody in secretions. The bacterial pathogen Streptococcus sanguis, a precursor to dental caries and a cause of bacterial endocarditis, yields IgA protease that cleaves only the Pro-Thr peptide bond in the left duplication, while the type 2 IgA proteases of the genital pathogen Neisseria gonorrhoeae and the respiratory pathogen Haemophilus influenzae cleave only the P-T bond in the right half. We have sequenced the entire S. sanguis iga gene cloned into Escherichia coli. A segment consisting of 20 amino acids tandemly repeated 10 times, of unknown function, occurs near the amino-terminal end of the enzyme encoded in E. coli. Identification of a predicted zinc-binding region in the S. sanguis enzyme and the demonstration that mutations in this region result in production of a catalytically inactive protein support the idea that the enzyme is a metalloprotease. The N. gonorrhoeae and H. influenzae enzymes were earlier shown to be serine-type proteases, while the Bacteroides melaninogenicus IgA protease was shown to be a cysteine-type enzyme. The streptococcal IgA protease amino acid sequence has no significant homology with either of the two previously determined IgA protease sequences, that of type 2 N. gonorrhoeae and type 1 H. influenzae. The differences in both structure and mechanism among these functionally analogous enzymes underscore their role in the infectious process and offer some prospect of therapeutic intervention.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Reference59 articles.
1. Inhibition of IgAl proteases from Neisseria gonorrhoeae and Haemophilus influenzae by peptide prolyl boronic acids;Bachovchin W. W.;J. Biol. Chem.,1990
2. Introduction: the classificatin of proteinases;Barrett A. J.;CIBA Found. Symp.,1980
3. Berman M. L. L. W. Enquist and T. J. Silhavy. 1984. Experiments with gene fusions. Cold Spring Harbor Laboratory Cold Spring Harbor N.Y.
4. A rapid alkaline extraction procedure for screening recombinant plasmid DNA;Birnboim H.;Nucleic Acids Res.,1979
5. Intracellular proteases. Annu;Bond J. S.;Rev. Biochem.,1987
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