Isvoran Adriana, Peng Yunhui, Ceauranu Silvana, Schmidt Leon, Nicot Arnaud B, Miteva Maria A
Department of Biology-Chemistry and Advanced Environmental Research Laboratories, West University of Timisoara, 16 Pestalozzi, 300115 Timisoara, Romania.
INSERM U1268 Medicinal Chemistry and Translational Research, CiTCoM UMR 8038 CNRS - Université Paris Cité, 75006 Paris, France.
Drug Discov Today. 2022 Nov;27(11):103349. doi: 10.1016/j.drudis.2022.103349. Epub 2022 Sep 9.
Sulfotransferases (SULTs) are Phase II drug-metabolizing enzymes (DMEs) catalyzing the sulfation of a variety of endogenous compounds, natural products, and drugs. Various drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDS) can inhibit SULTs, affecting drug-drug interactions. Several polymorphisms have been identified for SULTs that might be crucial for interindividual variability in drug response and toxicity or for increased disease risk. Here, we review current knowledge on non-synonymous single nucleotide polymorphisms (nsSNPs) of human SULTs, focusing on the coded SULT allozymes and molecular mechanisms explaining their variable activity, which is essential for personalized medicine. We discuss the structural and dynamic bases of key amino acid (AA) variants implicated in the impacts on drug metabolism in the case of SULT1A1, as revealed by molecular modeling approaches.
磺基转移酶（SULTs）是II相药物代谢酶（DMEs），可催化多种内源性化合物、天然产物和药物的硫酸化反应。各种药物，如非甾体抗炎药（NSAIDs），可抑制磺基转移酶，影响药物相互作用。已鉴定出磺基转移酶的几种多态性，这些多态性可能对个体间药物反应和毒性的差异或疾病风险增加至关重要。在此，我们综述了关于人类磺基转移酶非同义单核苷酸多态性（nsSNPs）的现有知识，重点关注编码的SULT同工酶以及解释其可变活性的分子机制，这对个性化医疗至关重要。我们讨论了分子建模方法揭示的SULT1A1中与药物代谢影响相关的关键氨基酸（AA）变体的结构和动力学基础。
