Highly Similar Sequences of Mature IgA1 Proteases from Neisseria meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae.

The mature serine-type IgA1 protease from Neisseria meningitidis serogroup B strain H44/76 (IgA1pr1_28-1004) is considered here as the basis for creating a candidate vaccine against meningococcal meningitis. In this work, we examine the primary structure similarity of IgA1 proteases from various strains of a number of Gram-negative bacteria (N. meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae) in order to find a structural groundwork for creating a broad-spectrum vaccine based on fragments of this enzyme. BLAST has shown high similarity between the primary structure of IgA1pr1_28-1004 and hypothetical sequences of mature IgA1 proteases from N. meningitidis (in 1060 out of 1061 examined strains), N. gonorrhoeae (in all 602 examined strains) and H. influenzae (in no less than 137 out of 521 examined strains). For these enzymes, common regions of sequence correspond to IgA1pr1_28-1004 fragments 28-84, 146-193, 253-539, 567-628, 639-795 and 811-1004, with identity of at least 85%. We believe that these fragments can be used in the development of a vaccine to prevent diseases caused by pathogenic strains of N. meningitidis and N. gonorrhoeae as well as a significant number of strains of H. influenzae.

Protective potency of recombinant meningococcal IgA1 protease and its structural derivatives upon animal invasion with meningococcal and pneumococcal infections.

Immunization of mice with recombinant IgA1 protease of Neisseria meningitidis or several structural derivatives thereof protects the animals infected with a variety of deadly pathogens, including N. meningitidis serogroups A, B, and C and 3 serotypes of Streptococcus pneumonia. In sera of rabbits immunized with inactivated pneumococcal cultures, antibodies binding IgA1-protease from N. meningitidis serogroup B were detected. Thus, the cross-reactive protection against meningococcal and pneumococcal infections has been demonstrated in vivo. Presumably it indicates the presence of common epitopes in the N. meningitidis IgA1 protease and S. pneumoniae surface proteins.

Hydrolases: the correlation between informational structure and the catalytic sites organization.

The novel method allowing identification of protein structure elements responsible for catalytic activity manifestation is proposed. Structural organization of various hydrolases was studied using the ANIS (ANalysis of Informational Structure) method. ANIS allows to reveal a hierarchy of the ELements of Information Structure (ELIS) using protein amino acid sequence. The ELIS corresponds to the variable length sites with an increased density of structural information. The amino acid residues forming the enzyme catalytic site were shown to belong to the different top-ranking ELIS located in the contact area of the corresponding spatial structure clusters. In the protein spatial structure catalytic sites are located in the area of contact between fragments of polypeptide chain (structural blocs) allocation to the different top-ranking ELIS. According to our results we concluded that structural blocks corresponding to top-ranking ELIS are crucial for protein functioning. Such regions are structurally independent, and their determinate mobility relative to each other is vital for an efficient enzymatic reaction to occur.