TYW1B Inhibitors

Chemical inhibitors of TYW1B utilize a variety of mechanisms to inhibit the function of this enzyme, which is essential for the modification of wybutosine in tRNA. Resveratrol targets TYW1B by obstructing the enzyme's ability to interact with the requisite tRNA substrate, effectively halting the modification process that is critical for tRNA maturation. Similarly, epigallocatechin gallate (EGCG) binds to the active site of TYW1B, preventing it from catalyzing the wybutosine synthesis pathway. This binding not only inhibits the current enzymatic action but also precludes future interactions with tRNA substrates. Curcumin plays a role in the inhibition of TYW1B by disrupting cellular pathways that are supportive of the enzyme's action on tRNA, thereby indirectly suppressing its activity. Another flavonoid, quercetin, competes with the tRNA substrate for binding sites on TYW1B, which reduces the enzyme's ability to engage in the modification process.

Continuing with the theme of flavonoids, genistein inhibits TYW1B by obstructing the ATP binding site, which is a prerequisite for the enzyme's activation and function. Without access to ATP, TYW1B cannot proceed with the modification of tRNA. Silibinin and silymarin, both found in milk thistle, contribute to the inhibition of TYW1B through different mechanisms. Silibinin alters the enzyme's conformation, rendering it less effective at interacting with its substrate. Silymarin, on the other hand, disrupts the cellular conditions necessary for TYW1B's activity, particularly affecting the pathways that facilitate the enzyme's interaction with tRNA. Luteolin and apigenin, two other flavonoids, inhibit TYW1B by targeting distinct enzyme domains essential for tRNA interaction; luteolin binds to the wybutosine-synthesizing domain while apigenin targets the tRNA recognition site. This binding prevents TYW1B from performing its tRNA modification function. Fisetin changes the oxidation state of necessary cofactors for TYW1B, which is crucial for its catalytic activity. Ellagic acid contributes to the inhibition by chelating metal ions that serve as cofactors, thus impairing TYW1B's catalytic capacity. Lastly, baicalein disrupts the substrate recognition of TYW1B, which diminishes its ability to catalyze the critical modification of wybutosine in tRNA. Each chemical, through its unique interaction with either the enzyme, its substrate, or the cellular environment, ensures the inhibition of TYW1B's role in tRNA modification.