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. (1st October 2014)

• Record Type: Journal Article
• Authors: Williams, Allison H.; Veyrier, Frédéric J.; Bonis, Mathilde; Michaud, Yann; Raynal, Bertrand; Taha, Muhamed‐Kheir; White, Stephen W.; Haouz, Ahmed; Boneca, Ivo G.
• Is Part Of: Acta crystallographica. Volume 70:Part 10(2014:Oct.)
• Page Start: 2631
• Page End: 2639
• Publication Date: 2014-10-01
• Subjects: Biomolecules -- Structure -- Periodicals; Physical biochemistry -- Periodicals; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; 572
• DOI: 10.1107/S1399004714016770
• Languages: English
• ISSNs: 0907-4449

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Peptidoglycan <italic>O</italic>‐acetylesterase (Ape1), which is required for host survival in <italic>Neisseria</italic> 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.</p> </abstract>