1x7o
From Proteopedia
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Crystal structure of the SpoU Methyltransferase AviRb from Streptomyces viridochromogenes
Overview
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.
About this Structure
1X7O is a Single protein structure of sequence from Streptomyces viridochromogenes. Full crystallographic information is available from OCA.
Reference
Structure and function of the antibiotic resistance-mediating methyltransferase AviRb from Streptomyces viridochromogenes., Mosbacher TG, Bechthold A, Schulz GE, J Mol Biol. 2005 Jan 21;345(3):535-45. PMID:15581897
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