Crystallography and activity studies provide invaluable information on how glycoside hydrolase (GH) enzymes break down glycosidic bonds on a subsecond timescale at ambient temperatures, despite these remarkably strong bonds having an estimated half-life on the order of millions of years. This experimental data has been the basis of hypothesized reaction mechanisms that have proven to be consistent for many, but not all, GH enzymes classified into families, as tracked on the CAZy website (www.cazy.org). To better understand these important carbohydrate-active enzymes, our group uses a range of computational techniques, including molecular dynamics (MM and QM/MM) simulations, enhanced sampling methods, and data science techniques to reveal elusive mechanisms and protein structure-function relationships. This presentation will include insights into the elusive mechanism of a GH family 6 cellulase, and the role of a puzzlingly inactive GH family 9 enzyme. These studies help understand enzymatic activities that defy chemical intuition and improve our efforts toward rational enzyme design.

Solving puzzles of glycoside hydrolase reaction mechanisms

255th National Meeting (2018)

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