Substrate-assisted catalysis unifies two families of chitinolytic enzymes

Tews, Ivo, Terwisscha Van Scheltinga, Anke C., Perrakis, Anastassis, Wilson, Keith S. and Dijkstra, Bauke W. (1997) Substrate-assisted catalysis unifies two families of chitinolytic enzymes. Journal of the American Chemical Society, 119 (34), 7954-7959. (doi:10.1021/ja970674i).

Abstract

Hen egg-white lysozyme has long been the paradigm for enzymatic glycosyl hydrolysis with retention of configuration, with a protonated carboxylic acid and a deprotonated carboxylate participating in general acid-base catalysis. In marked contrast, the retaining chitin degrading enzymes from glycosyl hydrolase families 18 and 20 all have a single glutamic acid as the catalytic acid but lack a nucleophile on the enzyme. Both families have a catalytic (βα)₈-barrel domain in common. X-ray structures of three different chitinolytic enzymes complexed with substrates or inhibitors identify a retaining mechanism involving a protein acid and the carbonyl oxygen atom of the substrate's C2 N-acetyl group as the nucleophile. These studies unambiguously demonstrate the distortion of the sugar ring toward a sofa conformation, long postulated as being close to that of the transition state in glycosyl hydrolysis.

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Contributors

Author: Ivo Tews

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