Structural and biochemical analyses of the tetrameric cell binding domain of Lys170 from enterococcal phage F170/08

Lysins are a class of hydrolytic enzymes used by bacteriophages to target and cleave the peptidoglycan of bacterial cell walls during their lytic cycle. The lysins from bacteriophages that infect Gram-positive bacteria are typically monomeric and consist of one or two catalytic domains (CD) and a cell binding domain (CBD). However, multimeric lysins encoded by a single gene have also been reported, among which Lys170 from enterococcal phage F170/08 was one of the first identified. Here, we determined the crystal structure of Lys170 CBD at 1.40 Å resolution. The structure reveals that Lys170 CBDs assemble into a tetrameric functional unit and that each monomer folds into a three-stranded β-sheet core capped on each side by an α-helix. In addition, we identified key residues of Lys170 CBD involved in host cell binding. Our work provides a basis for designing highly efficient lysins targeting Enterococcus faecalis.