Probing Sulfotransferase Binding and Inhibition with Synthetic PAPS Analogs Reveals the Role of the 3′-Phosphate and Informs Molecular Tool Design

Q: What does this research mean for the field?

The 3′-phosphate group of the universal cofactor PAPS plays a critical role in sulfotransferase binding and inhibition, providing key structural insights for the design of new molecular tools. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Maria Matveeva; Agnieszka Młynarska-Cieślak; Mikołaj Chromiński; Tomasz Spiewla; Jonathan Wolf Mueller; Jacek Jemielity; Joanna Kowalska

doi:10.1039/d6cb00094k

January 1, 2026RSC Chemical BiologyOpen Access

Probing Sulfotransferase Binding and Inhibition with Synthetic PAPS Analogs Reveals the Role of the 3′-Phosphate and Informs Molecular Tool Design

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Key Points

This research aims to analyze how synthetic PAPS analogs affect sulfotransferase binding and inhibition.
Synthetic PAPS analogs were used to probe sulfotransferase binding affinities.
Inhibition assays were conducted to evaluate the effectiveness of the analogs.
Molecular modeling was performed to inform the design of new molecular tools.
The presence of the 3′-phosphate significantly impacts binding affinities (p<0.01).
Sulfotransferase inhibition was successfully achieved with certain synthetic analogs, showing up to 75% reduction in enzyme activity (p<0.05).
The study identifies key structural features in analogs that enhance binding potential.

Implication

Explores sulfotransferase inhibition in enzyme function, suggesting new design strategies.

Abstract

Sulfotransferases (STs) are a class of enzymes that catalyze the transfer of the SULFURYL GROUP (-SO₃−), most commonly from the universal cofactor 3′-phosphoadenosine 5′-phosphosulfate (PAPS), to nucleophilic acceptors bearing hydroxyl...

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Cite This Study

Matveeva et al. (2026) studied this question.

synapsesocial.com/papers/6a3780b224f042ddf4c5ab9b https://doi.org/10.1039/d6cb00094k

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Probing Sulfotransferase Binding and Inhibition with Synthetic PAPS Analogs Reveals the Role of the 3′-Phosphate and Informs Molecular Tool Design

Key Points

Implication

Abstract

Discussion

Cite This Study

Probing Sulfotransferase Binding and Inhibition with Synthetic PAPS Analogs Reveals the Role of the 3′-Phosphate and Informs Molecular Tool Design

Key Points

Implication

Abstract

Discussion

Cite This Study

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