Naslov
Structural basis for the methylation of G1405 in 16S rRNA by aminoglycoside resistance methyltransferase Sgm from an antibiotic producer: A diversity of active sites in m7G methyltransferases.

Autori
Husain, Nilofer ; Tkaczuk, Karolina ; Tulsidas, Shenoy Rajesh, Kaminska, Katarzyna ; Čubrilo, Sonja ; Maravić Vlahoviček, Gordana ; Bujnicki, Janusz and Sivaraman, Jayaraman

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts / Kovarik, Zrinka ; Varljen, Jadranka - Rijeka : Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2010

Skup
10th Congress of the Croatian Society of Biochemistry and Molecular Biology “The Secret Life of Biomolecules”

Mjesto i datum
Opatija, Hrvatska, 15.09.2010. - 18.09.2010

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
Antibiotic resistance; Methyltransferase; Sgm; Aminoglycosides; crystal structure

Sažetak
Sgm methyltransferase is a member of Arm family of enzymes that confer high level resistance to aminoglycoside antibiotics. Sgm was isolated from sisomicin producer Micromonospora zionensis, where it helps to protect the cell from the toxic effect of the antibiotic. Sgm renders aminoglycoside resistance by methylating G1405 in 16S rRNA to m7G, which interferes with the antibiotic binding site on the ribosome. Genes encoding members of Arm family were recently found to spread among human pathogens cultured from nosocomial infections and animal isolates. The objective of this study was to examine the relationship between Arm enzymes found in antibiotic producers and those that emerged in resistant pathogens, as well as to make comparisons between active sites of different enzymes that introduce the m7G modification in RNA. In our previous work, we have made theoretical predictions of the Sgm structure and identified amino-acid residues responsible for catalysis. In this work we solved the crystal structure of Sgm in complex with cofactors AdoMet and AdoHcy at 2.0 and 2.1A˚ resolutions respectively. Structure-guided mutagenesis, isothermal titration calorimetry and protein–RNA footprinting enabled us to develop a model of Sgm–rRNA interactions and explain its mechanism of m7G1405 methylation in 16S rRNA. These findings will set the basis for the synthesis of the inhibitors of the Arm family members and in order to incapacitate the resistance of the pathogens.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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