1x7o
From Proteopedia
Crystal structure of the SpoU Methyltransferase AviRb from Streptomyces viridochromogenes
Structural highlights
Function[AVRB_STRVR] Specifically methylates the 2'-O-ribose position of uridine-2479 in 23S ribosomal RNA. Confers resistance to antibiotic avilamycin, an orthosomycin antibiotic.[1] [2] Evolutionary ConservationCheck, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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