1X7O

Crystal structure of the SpoU Methyltransferase AviRb from Streptomyces viridochromogenes

Summary for 1X7O

• Entry DOI: 10.2210/pdb1x7o/pdb
• Related: 1X7P
• Descriptor: rRNA methyltransferase (2 entities in total)
• Functional Keywords: spou, c-terminal knot, semet, transferase
• Biological source: Streptomyces viridochromogenes
• Total number of polymer chains: 2
• Total formula weight: 63159.45

Authors

Mosbacher, T.G.,Bechthold, A.,Schulz, G.E. (deposition date: 2004-08-16, release date: 2005-01-25, Last modification date: 2024-10-30)

Primary citation

Mosbacher, T.G.,Bechthold, A.,Schulz, G.E.
Structure and function of the antibiotic resistance-mediating methyltransferase AviRb from Streptomyces viridochromogenes
J.Mol.Biol., 345:535-545, 2005

PubMed Abstract: The emergence of antibiotic-resistant bacterial strains is a widespread problem in medical practice and drug design, and each case requires the elucidation of the underlying mechanism. AviRb from Streptomyces viridochromogenes methylates the 2'-O atom of U2479 of the 23S ribosomal RNA in Gram-positive bacteria and thus mediates resistance to the oligosaccharide (orthosomycin) antibiotic avilamycin. The structure of AviRb with and without bound cofactor S-adenosyl-L-methionine (AdoMet) was determined, showing that it is a homodimer belonging to the SpoU family within the SPOUT class of methyltransferases. The relationships within this class were analyzed in detail and, in addition, a novel fourth SpoU sequence fingerprint is proposed. Each subunit of AviRb consists of two domains. The N-terminal domain, being related to the ribosomal proteins L30 and L7Ae, is likely to bind RNA. The C-terminal domain is related to all SPOUT methyltransferases, and is responsible for AdoMet-binding, catalysis and dimerization. The cofactor binds at the characteristic knot of the polypeptide in an unusually bent conformation. The transferred methyl group points to a broad cleft formed with the L30-type domain of the other subunit. Measurements of mutant activity revealed four important residues responsible for catalysis and allowed the modeling of a complex between AviRb and the RNA target. The model includes a specificity pocket for uracil but does not contain a base for deprotonating the 2'-O atom of U2479 on methylation.

PubMed: 15581897
DOI: 10.1016/j.jmb.2004.10.051

Experimental method

X-RAY DIFFRACTION (2.37 Å)