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

Area of Science:

• Biochemistry
• Structural Biology
• Bioinformatics

Background:

• Amino acid mutations near enzyme active sites alter activity.
• Distal mutations (>10 Å from active site) also significantly impact enzyme function.
• Understanding distal mutation effects is challenging due to limited structural data.

Purpose of the Study:

• To create a comprehensive database, D3DistalMutation, linking distal mutations to enzyme activity changes.
• To analyze the impact of distal mutations on enzyme activity.
• To provide structural insights into enzyme regulation by distal mutations.

Main Methods:

• Construction of the D3DistalMutation database.
• Analysis of mutation data within the database.
• Examination of enzyme structures and pockets.

Main Results:

• Approximately 80% of distal mutations affect enzyme activity.
• 72.7% of distal mutations decrease or abolish enzyme activity.
• 6.6% of distal mutations increase enzyme activity, with Y>F, S>D, T>D being notable.

Conclusions:

• Distal mutations are crucial regulators of enzyme activity.
• The D3DistalMutation database facilitates research in enzyme engineering and allosteric drug design.
• Specific mutations offer potential for industrial catalysis and therapeutic development.