Pregled bibliografske jedinice broj: 368311
Identification of potential inhibitors of macrolide resistance methyltransferase ErmC by virtual screening and experimental analysis
Identification of potential inhibitors of macrolide resistance methyltransferase ErmC by virtual screening and experimental analysis // Book of abstracts / Strelec, Ivica ; Glavaš-Obrovac, Ljubica (ur.).
Osijek: Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2008. (poster, domaća recenzija, sažetak, znanstveni)
CROSBI ID: 368311 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
Identification of potential inhibitors of macrolide resistance methyltransferase ErmC by virtual screening and experimental analysis
Autori
Feder, Marcin ; Purta, Elzbieta ; Koscinski, Lukasz ; Čubrilo, Sonja ; Maravić Vlahoviček, Gordana ; Bujnicki, Janusz M.
Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni
Izvornik
Book of abstracts
/ Strelec, Ivica ; Glavaš-Obrovac, Ljubica - Osijek : Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2008
ISBN
978-953-95551-2-0
Skup
Congress of the Croatian Society for Biochemistry and Molecular Biology with international participation
Mjesto i datum
Osijek, Hrvatska, 17.09.2008. - 20.09.2008
Vrsta sudjelovanja
Poster
Vrsta recenzije
Domaća recenzija
Ključne riječi
macrolide antibiotics; antibiotic resistance; Erm methlytransferases; inhibitors
Sažetak
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.
Izvorni jezik
Engleski
Znanstvena područja
Biologija
POVEZANOST RADA
Projekti:
006-0982913-1219 - Molekularne osnove djelovanja antibiotika i mehanizmi bakterijske rezistencije (Maravić Vlahoviček, Gordana, MZOS ) ( CroRIS)
Ustanove:
Farmaceutsko-biokemijski fakultet, Zagreb