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The enzymes involved in the pathogenesis of viridans streptococcal infections, including streptococcal pyrogenic exotoxin A, streptococcal hemolysin, streptococcal hyaluronidase, and Streptococcal cytolysin, are oligomeric enzymes consisting of multiple copies of non-catalytic subunits (monomers) and catalytic subunits. The natural viridans streptococcal peptidoglycan hydrolases (VSPGHs) have a single catalytic subunit, some of which display notable structural characteristics that the third domain in the structures of dimeric enzymes is in an inactive state and may act as a molecular trap. Using the structure of Streptococcus pyogenes viridans (SPV) VSPGH1 as a scaffold, we show that residues proximal to the catalytic subunit in dimeric enzymes may influence substrate accessibility to the active site of the catalytic subunit. Our results suggest that a peptidoglycan hydrolase (PGH) may act as an efficient “molecular micromanipulator” to locally change substrate conformation and achieve a favored orientation with the catalytic subunit to gain access to a highly reactive enzyme-substrate complex. $date = date(‘Y-m-d’, strtotime($datestr[$

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