X-ray crystal structure of the streptococcal specific phage lysin PlyC.

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TitleX-ray crystal structure of the streptococcal specific phage lysin PlyC.
Publication TypeJournal Article
Year of Publication2012
AuthorsMcGowan, S, Buckle, AM, Mitchell, MS, Hoopes, JT, D Gallagher, T, Heselpoth, RD, Shen, Y, Reboul, CF, Law, RHP, Fischetti, VA, Whisstock, JC, Nelson, DC
JournalProc Natl Acad Sci U S A
Date Published2012 Jul 31
KeywordsCrystallography, X-Ray, Enzymes, Protein Structure, Quaternary, Protein Structure, Tertiary, Streptococcus equi, Streptococcus Phages, Viral Proteins

Bacteriophages deploy lysins that degrade the bacterial cell wall and facilitate virus egress from the host. When applied exogenously, these enzymes destroy susceptible microbes and, accordingly, have potential as therapeutic agents. The most potent lysin identified to date is PlyC, an enzyme assembled from two components (PlyCA and PlyCB) that is specific for streptococcal species. Here the structure of the PlyC holoenzyme reveals that a single PlyCA moiety is tethered to a ring-shaped assembly of eight PlyCB molecules. Structure-guided mutagenesis reveals that the bacterial cell wall binding is achieved through a cleft on PlyCB. Unexpectedly, our structural data reveal that PlyCA contains a glycoside hydrolase domain in addition to the previously recognized cysteine, histidine-dependent amidohydrolases/peptidases catalytic domain. The presence of eight cell wall-binding domains together with two catalytic domains may explain the extraordinary potency of the PlyC holoenyzme toward target bacteria.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID22807482
PubMed Central IDPMC3412044
Grant ListAI11822 / AI / NIAID NIH HHS / United States