Polysialic acid-degrading endosialidase
Bacteriophages or phages are viruses that infect bacteria. They are parasites that replicate inside the bacterial cell and made up of proteins and nucleic acid. The proteins form a protective shell, called a capsid, which encloses the nucleic acid genome, either DNA or RNA. Some phages also have tails or other appendages attached to the capsid, which help them bind to the host bacteria and transfer their genetic material into the bacterial cell. On entering the cell, the DNA or RNA is replicated to produce several copies of the phage genome. Other proteins required for the assembly of the phage progeny are also produced. The phage progeny are then assembled in the bacterial cell and released from it by the bursting or lysis of the host in most cases. E. coli K1 is a neuroinvasive bacterium that causes neonatal sepsis and meningitis. The bacteriophage K1F infects the E. coli K1 bacterium by degrading or cleaving the polysialic acid (polySia) capsule that protects it. The bacteriophage has a capsule degrading tailspike known as endosialidase. Thus endosialidases can be used in the treatment of meningitis and therapy of polySia-bearing tumors. Endosialidases are also widely used in polySia related neurosciences and cancer research.
The structure shown here is that of endosialidase NF. It is composed of three subunits forming a mushroom shaped homo-trimer. Each subunit in turn consists of three domains; the C-terminal domain forms a triple beta-helix forming which makes up the stalk of the mushroom whereas the N-terminal beta-barrel and the beta-propeller domains form the cap of the mushroom. The beta-propeller domain, which contains the catalytic site, is very similar to that of bacterial and eukaryotic exosialidases. The active site, however, shows marked differences, missing a few key residues strictly conserved among exosialidases. Two binding sites for sialic acid, one in the stalk region and another on the beta-barrel domain, are identified in the complex structure. It is possible that polymeric sialic acid might bind to both the binding sites simultaneously while it is being cleaved by the active site.
Protein Data Bank (PDB)
author: Ashwini Patil