Enzymes constitute a large fraction of genomes – 20% in humans – which makes them a very important part of life. Despite decades of studies and a rich literature dedicated to understanding the reaction mechanisms of enzymes, the rules of enzyme catalysis are still not fully clear.

A new tool, called EzMechanism, developed by the Thornton group at EMBL-EBI and described in a recent Nature Methods paper, has made progress towards predicting the mechanisms of enzymes that have not been characterised yet. 

What is an enzyme mechanism?

The catalytic mechanism is the sequence of steps that explain how a reaction proceeds in the active site of an enzyme.

The authors derived a set of rules for enzyme catalysis from the Mechanism and Catalytic Site Atlas (M-CSA), a database which has captured mechanisms for over 700 enzymes using scientific literature. They then used the rules to propose possible mechanisms, and validated them, to see whether the rules were predictive. 

“EzMechanism is a great starting point for researchers studying enzyme mechanisms because it quickly produces relevant suggestions based on scientific literature,” explained António Ribeiro, Researcher at the University of Porto, Portugal.

EzMechanism aims to answer the question ‘given an enzyme whose reaction and structure we know, can we predict its mechanism?’

A better understanding of enzyme mechanisms would be useful for a range of applications including drug development, and pesticides, and would support the design of new enzymes for food processing, biofuels, paper and pulp.

 “Enzymes perform the chemistry of life, so understanding what functions they fulfil and how they do it makes for fascinating research,” said Janet Thornton Research Group Leader and Director Emeritus at EMBL-EBI. 

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