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

• Published in: Acta crystallographica. Section D, Biological crystallography. Vol. 70; no. 10; pp. 2631 - 2639
• Main Authors: Williams, Allison H., Veyrier, Frédéric J., Bonis, Mathilde, Michaud, Yann, Raynal, Bertrand, Taha, Muhamed-Kheir, White, Stephen W., Haouz, Ahmed, Boneca, Ivo G.
• Format: Journal Article
• Language: English
• Published: 5 Abbey Square, Chester, Cheshire CH1 2HU, England International Union of Crystallography 01.10.2014; Wiley Subscription Services, Inc
• Subjects: Ape1; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Catalytic Domain; Crystal structure; Crystallography, X-Ray; Esterases - chemistry; Esterases - metabolism; Models, Molecular; Neisseria meningitidis - chemistry; Peptidoglycan - metabolism; peptidoglycan O-acetylesterase; Protein Conformation; Research Papers; SGNH hydrolase superfamily; Ape1; SGNH hydrolase superfamily; peptidoglycan O-acetylesterase
• ISSN: 1399-0047; 0907-4449; 1399-0047
• DOI: 10.1107/S1399004714016770

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.