Identification of potential inhibitors of macrolide resistance methyltransferase ErmC by virtual screening and experimental analysis (CROSBI ID 542362)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | domaća recenzija
Podaci o odgovornosti
Feder, Marcin ; Purta, Elzbieta ; Koscinski, Lukasz ; Čubrilo, Sonja ; Maravić Vlahoviček, Gordana ; Bujnicki, Janusz M.
engleski
Identification of potential inhibitors of macrolide resistance methyltransferase ErmC by virtual screening and experimental analysis
Widespread resistance to clinically important macrolide, lincosamide and streptogramin B antibiotics is often conferred by methyltransferases from the Erm family that catalyze S-adenosyl-L-methionine dependent modification of a specific adenine residue in bacterial 23S rRNA. Despite continuous efforts, thus far no inhibitors of these enzymes have been identified or designed that would effectively abolish this type of bacterial resistance. We used the crystal structure of ErmC' methyltransferase as a target for structure based virtual screening of a database comprising 58679 leadlike compounds. We selected 77 compounds for experimental validation ; 63 of them were predicted to bind to the catalytic pocket and 14 compounds were predicted to bind to the putative RNA binding site. Among them we found several novel inhibitors, which reduce the minimal inhibitory concentration of a macrolide antibiotic erythromycin for Escherichia coli with constitutively expressed ErmC' gene. Four of them have IC50 values in the micromolar range and can be regarded as new lead structures with the potential for further optimization, which would direct the development of clinically useful inhibitors and thus help to fight the macrolide resistance based on rRNA methylation.
macrolide antibiotics; antibiotic resistance; Erm methlytransferases; inhibitors
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Podaci o prilogu
102-x.
2008.
objavljeno
Podaci o matičnoj publikaciji
Book of abstracts
Strelec, Ivica ; Glavaš-Obrovac, Ljubica
Osijek: Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB)
978-953-95551-2-0
Podaci o skupu
Congress of the Croatian Society for Biochemistry and Molecular Biology with international participation
poster
17.09.2008-20.09.2008
Osijek, Hrvatska