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Fungal RNA polymerases are large multi-subunit enzymes that catalyze the DNA-dependent synthesis of all major classes of cellular RNAs—including mRNAs, rRNAs, tRNAs—in fungi. These enzymes function by binding promoter regions on DNA with assistance from various transcription factors and initiating chain elongation through nucleotide addition. The core catalytic mechanism involves conserved metal ion cofactors at the active site. While structurally similar across eukaryotes—including humans—fungal-specific features may exist that could be exploited therapeutically. Inhibitors such as Alpha-Amanitin demonstrate proof-of-concept that targeting these essential enzymes can be lethal to cells; however, selectivity remains a key challenge for drug development targeting pathogenic fungi without harming host cells.[1][3][5]
Inhibition of nucleotide addition during transcription elongation by binding to the active site or interfering with conformational changes required for catalysis[1][5]
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