Ribosomal protein L25, long-form / Ribosomal protein L25, beta domain / Ribosomal protein L25, C-terminal / Ribosomal protein TL5, C-terminal domain / Ribosomal protein L31 type A / Ribosomal protein L31 signature. / Ribosomal protein L31 / Ribosomal protein L31 superfamily / Ribosomal protein L31 / Ribosomal protein L21, conserved site ...Ribosomal protein L25, long-form / Ribosomal protein L25, beta domain / Ribosomal protein L25, C-terminal / Ribosomal protein TL5, C-terminal domain / Ribosomal protein L31 type A / Ribosomal protein L31 signature. / Ribosomal protein L31 / Ribosomal protein L31 superfamily / Ribosomal protein L31 / Ribosomal protein L21, conserved site / Ribosomal protein L21 signature. / Ribosomal protein L16 signature 1. / : / Ribosomal protein L6, conserved site / Ribosomal protein L6 signature 1. / Ribosomal protein L16, conserved site / Ribosomal protein L16 signature 2. / Ribosomal protein L9 signature. / Ribosomal protein L17 signature. / Ribosomal protein L9, bacteria/chloroplast / Ribosomal protein L9, C-terminal / Ribosomal protein L9, C-terminal domain / Ribosomal protein L9, C-terminal domain superfamily / Ribosomal L25p family / Ribosomal protein L25 / Ribosomal protein L28/L24 superfamily / Ribosomal protein L36 signature. / Ribosomal protein L25/Gln-tRNA synthetase, N-terminal / Ribosomal protein L25/Gln-tRNA synthetase, anti-codon-binding domain superfamily / Ribosomal protein L9, N-terminal domain superfamily / Ribosomal protein L9 / Ribosomal protein L9, N-terminal / Ribosomal protein L9, N-terminal domain / Ribosomal protein L28 / Ribosomal protein L35, conserved site / Ribosomal protein L35 signature. / Ribosomal protein L33, conserved site / Ribosomal protein L33 signature. / Ribosomal protein L35, non-mitochondrial / Ribosomal protein L5, bacterial-type / Ribosomal protein L6, bacterial-type / Ribosomal protein L18, bacterial-type / Ribosomal protein L19, conserved site / Ribosomal protein L19 signature. / Ribosomal protein L36 / Ribosomal protein L36 superfamily / Ribosomal protein L36 / Ribosomal protein L9/RNase H1, N-terminal / Ribosomal protein L20 signature. / Ribosomal protein L27, conserved site / Ribosomal protein L27 signature. / Ribosomal protein L14P, bacterial-type / Ribosomal protein L34, conserved site / Ribosomal protein L34 signature. / Ribosomal protein L22, bacterial/chloroplast-type / Ribosomal protein L35 / Ribosomal protein L35 superfamily / Ribosomal protein L2, bacterial/organellar-type / Ribosomal protein L35 / Ribosomal L28 family / Ribosomal protein L33 / Ribosomal protein L33 / Ribosomal protein L28/L24 / Ribosomal protein L33 superfamily / : / Ribosomal protein L30, bacterial-type / Ribosomal protein L16 / Ribosomal protein L18 / Ribosomal L18 of archaea, bacteria, mitoch. and chloroplast / L28p-like / Ribosomal protein L20 / Ribosomal protein L20 / Ribosomal protein L20, C-terminal / Ribosomal protein L21 / Ribosomal protein L27 / Ribosomal L27 protein / Ribosomal protein L19 / Ribosomal protein L19 superfamily / Ribosomal protein L19 / Ribosomal proteins 50S L24/mitochondrial 39S L24 / Ribosomal protein L17 / Ribosomal protein L17 superfamily / Ribosomal protein L17 / Ribosomal protein L21-like / L21-like superfamily / Ribosomal prokaryotic L21 protein / Ribosomal L32p protein family / Ribosomal protein L24 / Ribosomal protein L32p / Ribosomal protein L34 / Ribosomal protein L34 / Ribosomal protein L13, bacterial-type / Ribosomal protein L23/L25, conserved site / Ribosomal protein L3, bacterial/organelle-type / Ribosomal protein L15, bacterial-type / 50S ribosomal protein uL4 / Ribosomal protein L23 signature. / Ribosomal protein L30, conserved site / Ribosomal protein L29, conserved site / Ribosomal protein L30 signature. 類似検索 - ドメイン・相同性
Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL2 / Large ribosomal subunit protein uL22 / Large ribosomal subunit protein bL31 / Large ribosomal subunit protein uL14 / Large ribosomal subunit protein uL3 / Large ribosomal subunit protein bL33 / Large ribosomal subunit protein uL5 / Large ribosomal subunit protein bL28 / Large ribosomal subunit protein bL19 ...Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL2 / Large ribosomal subunit protein uL22 / Large ribosomal subunit protein bL31 / Large ribosomal subunit protein uL14 / Large ribosomal subunit protein uL3 / Large ribosomal subunit protein bL33 / Large ribosomal subunit protein uL5 / Large ribosomal subunit protein bL28 / Large ribosomal subunit protein bL19 / Large ribosomal subunit protein bL32 / Large ribosomal subunit protein uL29 / Large ribosomal subunit protein bL17 / Large ribosomal subunit protein uL16 / Large ribosomal subunit protein uL24 / Large ribosomal subunit protein uL4 / Large ribosomal subunit protein uL23 / Large ribosomal subunit protein bL25 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein uL18 / Large ribosomal subunit protein bL9 / Large ribosomal subunit protein bL27 / Large ribosomal subunit protein bL20 / Large ribosomal subunit protein bL35 / Large ribosomal subunit protein uL13 / 50S ribosomal protein L36 / 50S ribosomal protein L34 / 50S ribosomal protein L15 / Large ribosomal subunit protein bL21 類似検索 - 構成要素
National Natural Science Foundation of China (NSFC)
11179012
中国
National Natural Science Foundation of China (NSFC)
31725007
中国
National Basic Research Program of China (973 Program)
2011CB710800
中国
引用
ジャーナル: Emerg Microbes Infect / 年: 2022 タイトル: Cryo-EM structure of 50S ribosomal subunit bound with clarithromycin reveals dynamic and specific interactions with macrolides. 著者: Wen Zhang / ZhiFei Li / Yufan Sun / Peng Cui / Jianhua Liang / Qinghe Xing / Jing Wu / Yanhui Xu / Wenhong Zhang / Ying Zhang / Lin He / Ning Gao / 要旨: Tuberculosis (TB) is the leading infectious disease caused by (). Clarithromycin (CTY), an analog of erythromycin (ERY), is more potent against multidrug-resistance (MDR) TB. ERY and CTY were ...Tuberculosis (TB) is the leading infectious disease caused by (). Clarithromycin (CTY), an analog of erythromycin (ERY), is more potent against multidrug-resistance (MDR) TB. ERY and CTY were previously reported to bind to the nascent polypeptide exit tunnel (NPET) near peptidyl transferase center (PTC), but the only available CTY structure in complex with () ribosome could be misinterpreted due to resolution limitation. To date, the mechanism of specificity and efficacy of CTY for remains elusive since the ribosome-CTY complex structure is still unknown. Here, we employed new sample preparation methods and solved the ribosome-CTY complex structure at 3.3Å with cryo-EM technique, where the crucial gate site A2062 ( numbering) is located at the CTY binding site within NPET. Two alternative conformations of A2062, a novel -conformation as well as a swayed conformation bound with water molecule at interface, may play a role in coordinating the binding of specific drug molecules. The previously overlooked C-H hydrogen bond (H-bond) and π interaction may collectively contribute to the enhanced binding affinity. Together, our structure data provide a structural basis for the dynamic binding as well as the specificity of CTY and explain of how a single methyl group in CTY improves its potency, which provides new evidence to reveal previously unclear mechanism of translational modulation for future drug design and anti-TB therapy. Furthermore, our sample preparation method may facilitate drug discovery based on the complexes with low water solubility drugs by cryo-EM technique.
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基本情報
マップデータ
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機能・相同性情報
5S rRNA binding / 
データ登録者
中国, 3件 
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emd_31398.png
http://ftp.pdbj.org/pub/emdb/structures/EMD-31398
試料の構成要素
解析
電子顕微鏡法
