A comparative multivariate analysis of nitrilase enzymes: An ensemble based computational approach

Area of Science:

• Biochemistry
• Bioinformatics
• Evolutionary Biology

Background:

• Nitrilases catalyze nitrile hydrolysis, producing amides and acids.
• The nitrilase superfamily is found across diverse species, including bacteria, fungi, plants, and animals.
• Understanding nitrilase evolution and structure-function relationships is crucial for enzyme engineering.

Purpose of the Study:

• To perform a comparative computational analysis of nitrilases from various species.
• To investigate the evolutionary history, ecological connections, and structure-function associations of the nitrilase family.
• To identify conserved motifs and structural features contributing to nitrilase diversity.

Main Methods:

• Comparative genomics and motif analyses.
• Bayesian phylogenetic and structural analyses (molecular dynamics simulation, PCA, DCCM, RMSIP, FES).
• Analysis of coding gene sequences, amino acid sequences, and 3D structures.

Main Results:

• Nitrilase gene clusters are shared among bacteria, fungi, and plants, indicating evolutionary links.
• Catalytic site folding is conserved, but loop regions exhibit species-specific variations.
• Principal Component Analysis (PCA) shows nitrilases cluster into distinct clades due to side-chain variations, correlating with sequence and structure.

Conclusions:

• Bacterial nitrilases exhibit ecological and evolutionary relationships with fungi and plants, especially in plant-pathogen interactions.
• Sequence and structural variations, particularly in loop regions and side chains, explain nitrilase divergence.
• These findings provide insights for further research and improvement of industrially relevant nitrilase enzymes.