Impaired local hydrophobicity, structural stability and conformational flexibility due to point mutations in sult1 family of enzymes

Abstract

Sulfotransferases (SULTs) are enzymes involved in phase II of the metabolism of xenobiotics. Single nucleotide polymorphisms were identified for genes encoding the SULTs leading to allozymes with modified sulfating activity. This study aims to analyze the effects of the most frequently identified amino acid mutations in the sequences of enzymes belonging to the SULT1 family on their local properties and structural stability. The outcomes reveal that single point mutations alter the local hydrophobicity and flexibility, mainly due to destabilization of the protein structures, and consequently may lead to changes in the dynamic of the active site activity reducing the affinity for the substrate. Elucidation of how the single point mutations influence the activity of enzymes contributes to understanding the molecular basis of the specificity of enzymatic activity and mitigating anomalies in the metabolism of xenobiotics.