ArticleBiochemistry2012
A nucleotide-gated molecular pore selects sulfotransferase substrates.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- Allosteric Mechanisms Triggering Substrate and Cofactor Binding in the SULT1A1 Dimer as Revealed by Molecular Dynamics Simulations.Journal of chemical information and modeling · 2025Article
- Sulfotransferase 4A1 Coding Sequence and Protein Structure Are Highly Conserved in Vertebrates.Genes · 2024Review
- Role of Conformational Dynamics of Sulfotransferases SULT1A1 and SULT1A3 in Substrate Specificity.International journal of molecular sciences · 2023Article
- From Steroid and Drug Metabolism to Glycobiology, Using Sulfotransferase Structures to Understand and Tailor Function.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Insights into the substrate binding mechanism of SULT1A1 through molecular dynamics with excited normal modes simulations.Scientific reports · 2021Article
- Enzyme Kinetics of PAPS-Sulfotransferase.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Mechanistic Insights into the Effect of Ligands on Structural Stability and Selectivity of Sulfotransferase 2A1 (SULT2A1).ACS omega · 2019Article
- Effect of SULT2B1 genetic polymorphisms on the sulfation of dehydroepiandrosterone and pregnenolone by SULT2B1b allozymes.Molecular and cellular endocrinology · 2019Article
- Allosteres to regulate neurotransmitter sulfonation.The Journal of biological chemistry · 2019Article
- Isoform-specific therapeutic control of sulfonation in humans.Biochemical pharmacology · 2019Article
- The NSAID allosteric site of human cytosolic sulfotransferases.The Journal of biological chemistry · 2017Article
- Investigating the substrate binding mechanism of sulfotransferase 2A1 based on substrate tunnel analysis: a molecular dynamics simulation study.Journal of molecular modeling · 2016Article
- Isozyme Specific Allosteric Regulation of Human Sulfotransferase 1A1.Biochemistry · 2016Article
- Controlling Sulfuryl-Transfer Biology.Cell chemical biology · 2016Article
- Design and Interpretation of Human Sulfotransferase 1A1 Assays.Drug metabolism and disposition: the biological fate of chemicals · 2016Review
- Sulfotransferase 1A1 Substrate Selectivity: A Molecular Clamp Mechanism.Biochemistry · 2015Article
- The impact of ligands on the structure and flexibility of sulfotransferases: a molecular dynamics simulation study.Journal of molecular modeling · 2015Article
- Dimeric human sulfotransferase 1B1 displays cofactor-dependent subunit communication.Pharmacology research & perspectives · 2015Article
- The allosteric binding sites of sulfotransferase 1A1.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
- 3'-Phosphoadenosine 5'-phosphosulfate allosterically regulates sulfotransferase turnover.Biochemistry · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Human SULT2A1 is one of two predominant sulfotransferases in liver and catalyzes transfer of the sulfuryl moiety (-SO(3)) from activated sulfate (PAPS, 3'-phosphoadenosine 5-phosphosulfate) to hundreds of acceptors (metabolites and xenobiotics). Sulfation recodes the biologic activity of acceptors by altering their receptor interactions. The molecular basis on which these enzymes select and sulfonate specific acceptors from complex mixtures of competitors in vivo is a long-standing issue in the SULT field. Raloxifene, a synthetic steroid used in the prevention of osteoporosis, and dehydroepiandrosterone (DHEA), a ubiquitous steroid precusor, are reported to be sulfated efficiently by SULT2A1 in vitro, yet unlike DHEA, raloxifene is not sulfated in vivo. This selectivity was explored in initial rate and equilibrium binding studies that demonstrate pronounced binding antisynergy (21-fold) between PAPS and raloxifene, but not DHEA. Analysis of crystal structures suggests that PAP binding restricts access to the acceptor-binding pocket by restructuring a nine-residue segment of the pocket edge that constricts the active site opening, or "pore", that sieves substrates on the basis of their geometries. In silico docking predicts that raloxifene, which is considerably larger than DHEA, can bind only to the unliganded (open) enzyme, whereas DHEA binds both the open and closed forms. The predictions of these structures with regard to substrate binding are tested using equilibrium and pre-steady-state ligand binding studies, and the results confirm that a nucleotide-driven isomerization controls access to the acceptor-binding pocket and plays an important role in substrate selection by SULT2A1 and possibly other sulfotransferases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.