D3DistalMutation: a Database to Explore the Effect of Distal Mutations on Enzyme Activity

Enzyme activity is affected by amino
acid mutations, particularly
mutations near the active site. Increasing evidence has shown that
distal mutations more than 10 Å away from the active site may
significantly affect enzyme activity. However, it is difficult to
study the enzyme regulation mechanism of distal mutations due to the
lack of a systematic collection of three-dimensional (3D) structures,
highlighting distal mutation site and the corresponding enzyme activity
change. Therefore, we constructed a distal mutation database, namely,
D3DistalMutation, which relates the distal mutation to enzyme activity.
As a result, we observed that approximately 80% of distal mutations
could affect enzyme activity and 72.7% of distal mutations would decrease
or abolish enzyme activity in D3DistalMutation. Only 6.6% of distal
mutations in D3DistalMutation could increase enzyme activity, which
have great potential to the industrial field. Among these mutations,
the Y to F, S to D, and T to D mutations are most likely to increase
enzyme activity, which sheds some light on industrial catalysis. Distal
mutations decreasing enzyme activity in the allosteric pocket play
an indispensable role in allosteric drug design. In addition, the
pockets in the enzyme structures are provided to explore the enzyme
regulation mechanism of distal mutations. D3DistalMutation is accessible
free of charge at https://www.d3pharma.com/D3DistalMutation/index.php.