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Yorodumi- EMDB-31398: Cryo-EM structure of Mycobacterium tuberculosis 50S ribosome subu... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31398 | ||||||||||||
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Title | Cryo-EM structure of Mycobacterium tuberculosis 50S ribosome subunit bound with clarithromycin | ||||||||||||
Map data | The 50S ribosome subunit from Mycobacterium tuberculosis (Mtb) | ||||||||||||
Sample |
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Function / homology | Function and homology information large ribosomal subunit / 5S rRNA binding / transferase activity / tRNA binding / rRNA binding / ribosome / structural constituent of ribosome / ribonucleoprotein complex / translation / metal ion binding ...large ribosomal subunit / 5S rRNA binding / transferase activity / tRNA binding / rRNA binding / ribosome / structural constituent of ribosome / ribonucleoprotein complex / translation / metal ion binding / plasma membrane / cytoplasm Similarity search - Function | ||||||||||||
Biological species | Mycobacterium tuberculosis H37Ra (bacteria) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||||||||
Authors | Zhang W / Sun Y / Gao N / Li Z | ||||||||||||
Funding support | China, 3 items
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Citation | Journal: Emerg Microbes Infect / Year: 2022 Title: Cryo-EM structure of 50S ribosomal subunit bound with clarithromycin reveals dynamic and specific interactions with macrolides. Authors: Wen Zhang / ZhiFei Li / Yufan Sun / Peng Cui / Jianhua Liang / Qinghe Xing / Jing Wu / Yanhui Xu / Wenhong Zhang / Ying Zhang / Lin He / Ning Gao / Abstract: 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. | ||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_31398.map.gz | 166.8 MB | EMDB map data format | |
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Header (meta data) | emd-31398-v30.xml emd-31398.xml | 50.9 KB 50.9 KB | Display Display | EMDB header |
Images | emd_31398.png | 236.4 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31398 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31398 | HTTPS FTP |
-Related structure data
Related structure data | 7f0dMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_31398.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | The 50S ribosome subunit from Mycobacterium tuberculosis (Mtb) | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.04 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
+Entire : Mycobacterium tuberculosis ribosome 50S subunit
+Supramolecule #1: Mycobacterium tuberculosis ribosome 50S subunit
+Supramolecule #2: 50S ribosomal subunit
+Macromolecule #1: 50S ribosomal protein L32
+Macromolecule #2: 50S ribosomal protein L33
+Macromolecule #3: 50S ribosomal protein L34
+Macromolecule #4: 50S ribosomal protein L35
+Macromolecule #5: 50S ribosomal protein L36
+Macromolecule #6: 50S ribosomal protein L31
+Macromolecule #9: 50S ribosomal protein L2
+Macromolecule #10: 50S ribosomal protein L3
+Macromolecule #11: 50S ribosomal protein L4
+Macromolecule #12: 50S ribosomal protein L5
+Macromolecule #13: 50S ribosomal protein L6
+Macromolecule #14: 50S ribosomal protein L9
+Macromolecule #15: 50S ribosomal protein L13
+Macromolecule #16: 50S ribosomal protein L14
+Macromolecule #17: 50S ribosomal protein L15
+Macromolecule #18: 50S ribosomal protein L16
+Macromolecule #19: 50S ribosomal protein L17
+Macromolecule #20: 50S ribosomal protein L18
+Macromolecule #21: 50S ribosomal protein L19
+Macromolecule #22: 50S ribosomal protein L20
+Macromolecule #23: 50S ribosomal protein L21
+Macromolecule #24: 50S ribosomal protein L22
+Macromolecule #25: 50S ribosomal protein L23
+Macromolecule #26: 50S ribosomal protein L24
+Macromolecule #27: 50S ribosomal protein L25
+Macromolecule #28: 50S ribosomal protein L27
+Macromolecule #29: 50S ribosomal protein L28
+Macromolecule #30: 50S ribosomal protein L29
+Macromolecule #31: 50S ribosomal protein L30
+Macromolecule #7: 23S rRNA
+Macromolecule #8: 5S ribosomal RNA
+Macromolecule #32: CLARITHROMYCIN
+Macromolecule #33: MAGNESIUM ION
+Macromolecule #34: water
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: NITROGEN |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.5 µm |
Image recording | Film or detector model: GATAN K2 IS (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
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Final angle assignment | Type: ANGULAR RECONSTITUTION |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 34912 |