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Structure and function of RNase AS, a polyadenylate-specific exoribonuclease affecting mycobacterial virulence in vivo. | LitMetric
The cell-envelope of Mycobacterium tuberculosis plays a key role in bacterial virulence and antibiotic resistance. Little is known about the molecular mechanisms of regulation of cell-envelope formation. Here, we elucidate functional and structural properties of RNase AS, which modulates M. tuberculosis cell-envelope properties and strongly impacts bacterial virulence in vivo. The structure of RNase AS reveals a resemblance to RNase T from Escherichia coli, an RNase of the DEDD family involved in RNA maturation. We show that RNase AS acts as a 3'-5'-exoribonuclease that specifically hydrolyzes adenylate-containing RNA sequences. Also, crystal structures of complexes with AMP and UMP reveal the structural basis for the observed enzyme specificity. Notably, RNase AS shows a mechanism of substrate recruitment, based on the recognition of the hydrogen bond donor NH2 group of adenine. Our work opens a field for the design of drugs able to reduce bacterial virulence in vivo.
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