Structures of five antibiotics bound at the peptidyl transferase center of the large ribosomal subunit
Structures of five antibiotics bound at the peptidyl transferase center of the large ribosomal subunit
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DOI：
10.1016/s0022-2836(03)00668-5
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发表时间：
2003-07-25
影响因子：
5.6
通讯作者：
Steitz, TA
中科院分区：
文献类型：
--
作者：
Hansen, JL;Moore, PB;Steitz, TA
在3.0埃分辨率下，测定了与海僵菌核糖体大亚基结合的茴香霉素、氯霉素、司帕霉素、杀稻瘟菌素S和维吉尼亚霉素M的结构。这些抗生素中的大多数与肽基-tRNA或氨酰-tRNA的重叠位点结合，这与它们作为肽键形成的竞争性抑制剂的功能一致。两个疏水裂缝，一个在肽基转移酶中心，另一个在肽出口通道的入口处，在结合这些抗生素中发挥作用。在这些裂缝的中间，H. marismortui（2062 Escherichia coli）的构象不同，因此与结合在任一缝隙中的抗生素接触。茴香霉素的芳环与活性位点的疏水缝隙结合，嘌呤霉素的芳环也是如此，而氯霉素的芳环与出口通道的疏水缝隙结合。斯帕索霉素主要接触P-位点结合底物，但也延伸到活性位点疏水缝隙中。阿维菌素M占据A和P位点的部分，并诱导核糖体的构象变化。杀稻瘟菌素S与P环碱基配对，从而模拟P位点结合的tRNA的C74和C75。(C)2003 Elsevier Ltd.保留所有权利。
Structures of anisomycin, chloramphenicol, sparsomycin, blasticidin S, and virginiamycin M bound to the large ribosomal subunit of Haloarcula marismortui have been determined at 3.0 Angstrom resolution. Most of these antibiotics bind to sites that overlap those of either peptidyl-tRNA or aminoacyl-tRNA, consistent with their functioning as competitive inhibitors of peptide bond formation. Two hydrophobic crevices, one at the peptidyl transferase center and the other at the entrance to the peptide exit tunnel play roles in binding these antibiotics. Midway between these crevices, nucleotide A2103 of H. marismortui (2062 Escherichia coli) varies in its conformation and thereby contacts antibiotics bound at either crevice. The aromatic ring of anisomycin binds to the active-site hydrophobic crevice, as does the aromatic ring of puromycin, while the aromatic ring of chloramphenicol binds to the exit tunnel hydrophobic crevice. Sparsomycin contacts primarily a P-site bound substrate, but also extends into the active-site hydrophobic crevice. Virginiamycin M occupies portions of both the A and P-site, and induces a conformational change in the ribosome. Blasticidin S base-pairs with the P-loop and thereby mimics C74 and C75 of a P-site bound tRNA. (C) 2003 Elsevier Ltd. All rights reserved.