Pharmacogenetics of human sulfotransferases and impact of amino acid exchange on Phase II drug metabolism

Adriana Isvoran; Yunhui Peng; Silvana Ceauranu; Leon Schmidt; Arnaud B Nicot; Maria A Miteva

doi:10.1016/j.drudis.2022.103349

Pharmacogenetics of human sulfotransferases and impact of amino acid exchange on Phase II drug metabolism

Drug Discov Today. 2022 Nov;27(11):103349. doi: 10.1016/j.drudis.2022.103349. Epub 2022 Sep 9.

Authors

Adriana Isvoran¹, Yunhui Peng², Silvana Ceauranu¹, Leon Schmidt¹, Arnaud B Nicot³, Maria A Miteva⁴

Affiliations

¹ Department of Biology-Chemistry and Advanced Environmental Research Laboratories, West University of Timisoara, 16 Pestalozzi, 300115 Timisoara, Romania.
² INSERM U1268 Medicinal Chemistry and Translational Research, CiTCoM UMR 8038 CNRS - Université Paris Cité, 75006 Paris, France.
³ INSERM, Nantes Université, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France. Electronic address: arnaud.nicot@inserm.fr.
⁴ INSERM U1268 Medicinal Chemistry and Translational Research, CiTCoM UMR 8038 CNRS - Université Paris Cité, 75006 Paris, France. Electronic address: maria.mitev@inserm.fr.

PMID: 36096358
DOI: 10.1016/j.drudis.2022.103349

Abstract

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.

Keywords: Drug metabolism; Drug–drug interactions; In silico modeling; Pharmacogenomics; Sulfotransferase.

Publication types

Review