Neuraminidase A from Streptococcus pneumoniae has a modular organization of catalytic and lectin domains separated by a flexible linker.

Neuraminidase A (NanA) of the pathogen Streptococcus pneumoniae cleaves receptors of the human respiratory epithelial surface during bacterial colonization. The full-size structure of NanA that contains one lectin and one catalytic domain within a single polypeptide chain remains unresolved. Both domains are crucial for the microorganism's virulence and considered as promising antimicrobial targets. Methods of bioinformatics and molecular dynamics have been implemented to model NanA's structure and study interaction between the lectin and catalytic domains in three neuraminidases NanA, NanB, and NanC from Streptococcus pneumoniae. A significant difference in spatial organization of these homologous enzymes has been revealed. The lectin and catalytic domains of NanB and NanC form rigid globules stabilized by multiple interdomain interactions, whereas in NanA, the two domains are separated by a 16 amino acids long flexible linker - a characteristic of proteins that require conformational flexibility for their functioning. The biological role of this structural adaptation of NanA as a key virulence enzyme is discussed.