Visualization of a substrate-induced productive conformation of the catalytic triad of the Neisseria meningitidis peptidoglycan O-acetylesterase reveals mechanistic conservation in SGNH esterase family members.

Peptidoglycan O-acetylesterase (Ape1), which is required for host survival in Neisseria sp., belongs to the diverse SGNH hydrolase superfamily, which includes important viral and bacterial virulence factors. Here, multi-domain crystal structures of Ape1 with an SGNH catalytic domain and a newly identified putative peptidoglycan-detection module are reported. Enzyme catalysis was performed in Ape1 crystals and key catalytic intermediates along the SGNH esterase hydrolysis reaction pathway were visualized, revealing a substrate-induced productive conformation of the catalytic triad, a mechanistic detail that has not previously been observed. This substrate-induced productive conformation of the catalytic triad shifts the established dogma on these enzymes, generating valuable insight into the structure-based design of drugs targeting the SGNH esterase superfamily.

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PDB reference: http://scripts.iucr.org/cgi-bin/cr.cgi?rm=pdb&pdbId=4k3u

PDB reference: http://scripts.iucr.org/cgi-bin/cr.cgi?rm=pdb&pdbId=4k9s

PDB reference: http://scripts.iucr.org/cgi-bin/cr.cgi?rm=pdb&pdbId=4k7j

PDB reference: http://scripts.iucr.org/cgi-bin/cr.cgi?rm=pdb&pdbId=4k40

Supporting Information. DOI: http://dx.doi.org/10.1107/S1399004714016770/cb5053sup1.pdf