Journal of the Serbian Chemical Society 2023 Volume 88, Issue 9, Pages: 841-857
https://doi.org/10.2298/JSC230210022C
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Impaired local hydrophobicity, structural stability and conformational flexibility due to point mutations in SULT1 family of enzymes
Ceauranu Silvana 
(Department of Biology-Chemistry and Advanced Environmental Research Laboratories, West University of Timisoara, Timisoara, Romania)
Ostafe Vasile (Department of Biology-Chemistry and Advanced Environmental Research Laboratories, West University of Timisoara, Timisoara, Romania)
Isvoran Adriana (Department of Biology-Chemistry and Advanced Environmental Research Laboratories, West University of Timisoara, Timisoara, Romania), [email protected]
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 analyse 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, may consequently 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.
Keywords: protein plasticity, protein stability, hydrophobicity profile, mutations, metabolism, bioinformatics
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