| Structural highlights
Function
[EXRBN_MYCTU] Exonuclease that cleaves single-stranded 3' overhangs of double-stranded RNA. Has no activity with 5' overhangs. Has negligible endonuclease activity. Can bind ATP, dATP and AMP (in vitro); the nucleotide occupies the predicted substrate binding site.[1]
Publication Abstract from PubMed
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.
Structure and Function of RNase AS, a Polyadenylate-Specific Exoribonuclease Affecting Mycobacterial Virulence In Vivo.,Romano M, van de Weerd R, Brouwer FC, Roviello GN, Lacroix R, Sparrius M, van den Brink-van Stempvoort G, Maaskant JJ, van der Sar AM, Appelmelk BJ, Geurtsen JJ, Berisio R Structure. 2014 May 6;22(5):719-30. doi: 10.1016/j.str.2014.01.014. Epub 2014 Apr, 3. PMID:24704253[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Abendroth J, Ollodart A, Andrews ES, Myler PJ, Staker BL, Edwards TE, Arcus VL, Grundner C. Mycobacterium tuberculosis Rv2179c establishes a new exoribonuclease family with broad phylogenetic distribution. J Biol Chem. 2013 Dec 4. PMID:24311791 doi:http://dx.doi.org/10.1074/jbc.M113.525683
- ↑ Romano M, van de Weerd R, Brouwer FC, Roviello GN, Lacroix R, Sparrius M, van den Brink-van Stempvoort G, Maaskant JJ, van der Sar AM, Appelmelk BJ, Geurtsen JJ, Berisio R. Structure and Function of RNase AS, a Polyadenylate-Specific Exoribonuclease Affecting Mycobacterial Virulence In Vivo. Structure. 2014 May 6;22(5):719-30. doi: 10.1016/j.str.2014.01.014. Epub 2014 Apr, 3. PMID:24704253 doi:http://dx.doi.org/10.1016/j.str.2014.01.014
|
