INTERACTION OF THE ANTIBIOTICS CLINDAMYCIN AND LINCOMYCIN WITH ESCHERICHIA-COLI 23S RIBOSOMAL-RNA
INTERACTION OF THE ANTIBIOTICS CLINDAMYCIN AND LINCOMYCIN WITH ESCHERICHIA-COLI 23S RIBOSOMAL-RNA
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DOI：
10.1093/nar/20.18.4717
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发表时间：
1992-09-25
影响因子：
14.9
通讯作者：
DOUTHWAITE, S
中科院分区：
文献类型：
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作者：
DOUTHWAITE, S
用化学足迹法比较了抗生素克林霉素和林可霉素与大肠杆菌核糖体的相互作用。两种药物提供的保护仅限于23 S rRNA的肽基转移酶环。在体外1 mM药物浓度的化学计量结合条件下，两种药物均强烈保护23 S rRNA碱基A2058和A2451免受硫酸二甲酯的影响，保护G2505免受酮醛修饰的影响; G2061也受到酮醛的微弱保护。修饰模式的不同之处在于A2059另外被克林霉素保护，而不是被林可霉素保护。通过足迹法估计的两种药物对核糖体的亲和力大致相同，林可霉素的K（diss）值为5 μ M，克林霉素为8 μ M。结果表明，在体外，药物在阻断其核糖体靶位点方面具有同等效力。然而，它们对肽键形成的抑制作用可能略有不同。
Interaction of the antibiotics clindamycin and lincomycin with Escherichia coli ribosomes has been compared by chemical footprinting. The protection afforded by both drugs is limited to the peptidyl transferase loop of 23S rRNA. Under conditions of stoichiometric binding at 1 mM drug concentration in vitro, both drugs strongly protect 23S rRNA bases A2058 and A2451 from dimethyl sulphate and G2505 from kethoxal modification; G2061 is also weakly protected from kethoxal. The modification patterns differ in that A2059 is additionally protected by clindamycin but not by lincomycin. The affinity of the two drugs for the ribosome, estimated by footprinting, is approximately the same, giving K(diss) values of 5 muM for lincomycin and 8 muM for clindamycin. The results show that in vitro the drugs are equally potent in blocking their ribosomal target site. Their inhibitory effects on peptide bond formation could, however, be subtly different.