How Do DICER1 Syndrome Mutations Disrupt Catalysis? Unveiling Dicer Metal Binding Architecture and Mechanism of Action Using MD Simulations and QM/MM Calculations.

Abstract excerpt

The RNA interference (RNAi) pathway regulates gene expression and viral defense and has been harnessed in therapeutic solutions to inhibit otherwise undruggable proteins by preventing translation. Dicer initiates RNAi by generating cleaved RNA products that bind to a target mRNA to promote gene silencing. Mutations to the Dicer catalytic domain cause DICER1 syndrome, which increases the risk of cancers, including...

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