Publications by authors named "Chun-I Tu"
In various autoimmune diseases, dysfunctional TREX1 (Three prime Repair Exonuclease 1) leads to accumulation of endogenous single-stranded DNA (ssDNA), double-stranded DNA (dsDNA) and DNA/RNA hybrids in the cytoplasm and triggers immune activation through the cGAS-STING pathway. Although inhibition of TREX1 could be a useful strategy for cancer immunotherapy, profiling cellular functions in terms of its potential substrates is a key step. Particularly important is the functionality of processing DNA/RNA hybrids and RNA substrates.
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- This study identifies PCMPS and PCMB as targeted covalent inhibitors of DEDDh exonucleases, which are significant for cancer and antiviral therapies.
- The research utilizes X-ray crystallography, binding assays, and molecular dynamics simulations to understand the binding sites and mechanisms of these compounds, particularly focusing on Cys409 and Cys461 in the Lassa fever virus NP exonuclease.
- Findings reveal that PCMPS induces allosteric inhibition, altering the RNA-binding lid's conformation, which is crucial for developing new TCIs as therapeutic agents.