Identification of specificity determining residues in enzymes using environment specific substitution tables

TL;DR

This paper presents a method that combines structure, sequence, and functional data to identify specificity determining residues in enzymes, aiding understanding of enzyme function and specificity.

Contribution

It introduces a novel scoring procedure leveraging environment specific substitution tables and structural alignments to predict enzyme SDRs.

Findings

Successfully predicts SDRs with validation from ligand data

Enhances understanding of enzyme specificity mechanisms

Integrates multiple data sources for improved accuracy

Abstract

Environment specific substitution tables have been used effectively for distinguishing structural and functional constraints on proteins and thereby identify their active sites (Chelliah et al. (2004)). This work explores whether a similar approach can be used to identify specificity determining residues (SDRs) responsible for cofactor dependence, substrate specificity or subtle catalytic variations. We combine structure-sequence information and functional annotation from various data sources to create structural alignments for homologous enzymes and functional partitions therein. We develop a scoring procedure to predict SDRs and assess their accuracy using information from bound specific ligands and published literature.