4OKE

Structure of RNase AS, a polyadenylate-specific exoribonuclease affecting mycobacterial virulence in vivo

Summary for 4OKE

• Entry DOI: 10.2210/pdb4oke/pdb
• Related: 4OKJ 4OKK
• Descriptor: 3'-5' exoribonuclease Rv2179c/MT2234.1, ADENOSINE MONOPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: m. tuberculosis, ribonuclease, capsular polysaccharides, virulence, hydrolase
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 2
• Total formula weight: 40166.87

Authors

Berisio, R.,Romano, M. (deposition date: 2014-01-22, release date: 2014-05-21, Last modification date: 2024-03-20)

Primary citation

Romano, M.,van de Weerd, R.,Brouwer, F.C.C.,Roviello, G.N.,Lacroix, R.,Sparrius, M.,van den Brink-van Stempvoort, G.,Maaskant, J.J.,van der Sar, A.M.,Appelmelk, B.J.,Geurtsen, J.J.,Berisio, R.
Structure and Function of RNase AS, a Polyadenylate-Specific Exoribonuclease Affecting Mycobacterial Virulence In Vivo
Structure, 22:719-730, 2014

PubMed Abstract: 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.

PubMed: 24704253
DOI: 10.1016/j.str.2014.01.014

Experimental method

X-RAY DIFFRACTION (1.7 Å)