The 1.6 Å Crystal Structure of the Catalytic Domain of PlyB, a Bacteriophage Lysin Active Against Bacillus anthracis

• Published in: Journal of molecular biology 2007-02, Vol.366 (2), p.540-550
• Main Authors: Porter, Corrine J., Schuch, Raymond, Pelzek, Adam J., Buckle, Ashley M., McGowan, Sheena, Wilce, Matthew C.J., Rossjohn, Jamie, Russell, Ryann, Nelson, Daniel, Fischetti, Vincent A., Whisstock, James C.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Bacillus anthracis; Bacillus anthracis - chemistry; Bacillus anthracis - virology; bacteriophage; Bacteriophages - chemistry; Binding Sites; Catalytic Domain; Crystallography, X-Ray; glycosyl hydrolase 25 family; lysin; Models, Molecular; Molecular Sequence Data; Mucoproteins - chemistry; Mucoproteins - genetics; Mucoproteins - isolation & purification; N-Glycosyl Hydrolases - chemistry; N-Glycosyl Hydrolases - genetics; N-Glycosyl Hydrolases - isolation & purification; peptidoglycan; Phage T7; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Structure-Activity Relationship; Substrate Specificity; Viral Proteins - chemistry; Viral Proteins - genetics; Viral Proteins - isolation & purification
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2006.11.056

Lysins are peptidoglycan hydrolases that are produced by bacteriophage and act to lyse the bacterial host cell wall during progeny phage release. Here, we describe the structure and function of a novel bacteriophage-derived lysin, PlyB, which displays potent lytic activity against the Bacillus anthracis-like strain ATCC 4342. This molecule comprises an N-terminal catalytic domain (PlyB cat) and a C-terminal bacterial SH3-like domain, SH3b. It is shown that both domains are required for effective catalytic activity against ATCC 4342. Further, PlyB has specific activity comparable to the phage lysin PlyG, an amidase being developed as a therapeutic against anthrax. In contrast to PlyG, however, the 1.6 Å X-ray crystal structure of PlyB cat reveals that the catalytic domain adopts the glycosyl hydrolase (GH)-25, rather than phage T7 lysozyme-like fold. PlyB therefore represents a new class of anthrax lysin and a new defensive tool in the armament against anthrax-mediated bioterrorism.