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

Sheena McGowan, Ashley M Buckle, Michael S Mitchell, James T Hoopes, D Travis Gallagher, Ryan D Heselpoth, Yang Shen, Cyril Florent Reboul, Ruby HP Law, Vincent A Fischetti, James C Whisstock, Daniel C Nelson

Research output: Contribution to journalArticleResearchpeer-review

55 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)12752 - 12757
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number31
DOIs
Publication statusPublished - 2012

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