Open AccessVisualization 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
Author(s) -
Williams Allison H.,
Veyrier Frédéric J.,
Bonis Mathilde,
Michaud Yann,
Raynal Bertrand,
Taha MuhamedKheir,
White Stephen W.,
Haouz Ahmed,
Boneca Ivo G.
Publication year - 2014
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
ISSN - 1399-0047
DOI - 10.1107/s1399004714016770
Subject(s) - catalytic triad , peptidoglycan , esterase , neisseria , hydrolase , substrate (aquarium) , enzyme , protein superfamily , catalysis , biology , biochemistry , protein structure , virulence , chemistry , microbiology and biotechnology , active site , bacteria , genetics , gene , ecology
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.