Courtesy of Vincent A. Fischetti
 ENIGMATIC ENZYME: Computer-generated ribbon model of the C-terminal end of the M protein sequence containing the conserved LPXTG motif (red). This region is also found in all C-terminal-anchored surface proteins from gram-positive bacteria.

Imagine an enzyme assembled from multiple peptides, each the product of a different gene. Imagine that of the 60 amino acids in the sequence, only 40 are identifiable in the standard repertoire; the others are novel in structure and are likely not assembled on the ribosome but by vast, cumbersome megaprotein complexes. Imagine that the completed enzyme is essential to the life of the bacterium and that an identified inhibitor may pave the way for a powerful new class of broad-spectrum antibiotics. Welcome to the strange world of LPXTGase.

Most surface proteins of Gram-positive bacteria possess a terminal LPXTG sequence that gets cleaved as the proteins journey across the cell septum for...

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