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Yorodumi- EMDB-12604: Cryo-EM structure of the mycolic acid transporter MmpL3 from M. t... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-12604 | |||||||||||||||||||||
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Title | Cryo-EM structure of the mycolic acid transporter MmpL3 from M. tuberculosis | |||||||||||||||||||||
Map data | sharpened map | |||||||||||||||||||||
Sample |
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Keywords | TRANSPORTER / MEMBRANE PROTEIN | |||||||||||||||||||||
Function / homology | Function and homology information phosphatidylglycerol binding / Actinobacterium-type cell wall biogenesis / diacylglycerol binding / cell tip / lipopolysaccharide transport / mycolic acid biosynthetic process / cell septum / cardiolipin binding / phosphatidylethanolamine binding / phosphatidylinositol binding ...phosphatidylglycerol binding / Actinobacterium-type cell wall biogenesis / diacylglycerol binding / cell tip / lipopolysaccharide transport / mycolic acid biosynthetic process / cell septum / cardiolipin binding / phosphatidylethanolamine binding / phosphatidylinositol binding / peptidoglycan-based cell wall / regulation of membrane potential / membrane => GO:0016020 / cell wall organization / response to antibiotic / plasma membrane Similarity search - Function | |||||||||||||||||||||
Biological species | Mycobacterium tuberculosis (bacteria) | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||||||||||||||
Authors | Adams O / Deme JC | |||||||||||||||||||||
Funding support | United Kingdom, 6 items
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Citation | Journal: Structure / Year: 2021 Title: Cryo-EM structure and resistance landscape of M. tuberculosis MmpL3: An emergent therapeutic target. Authors: Oliver Adams / Justin C Deme / Joanne L Parker / / Philip W Fowler / Susan M Lea / Simon Newstead / Abstract: Tuberculosis (TB) is the leading cause of death from a single infectious agent and in 2019 an estimated 10 million people worldwide contracted the disease. Although treatments for TB exist, continual ...Tuberculosis (TB) is the leading cause of death from a single infectious agent and in 2019 an estimated 10 million people worldwide contracted the disease. Although treatments for TB exist, continual emergence of drug-resistant variants necessitates urgent development of novel antituberculars. An important new target is the lipid transporter MmpL3, which is required for construction of the unique cell envelope that shields Mycobacterium tuberculosis (Mtb) from the immune system. However, a structural understanding of the mutations in Mtb MmpL3 that confer resistance to the many preclinical leads is lacking, hampering efforts to circumvent resistance mechanisms. Here, we present the cryoelectron microscopy structure of Mtb MmpL3 and use it to comprehensively analyze the mutational landscape of drug resistance. Our data provide a rational explanation for resistance variants local to the central drug binding site, and also highlight a potential alternative route to resistance operating within the periplasmic domain. | |||||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_12604.map.gz | 117.9 MB | EMDB map data format | |
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Header (meta data) | emd-12604-v30.xml emd-12604.xml | 17.4 KB 17.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_12604_fsc.xml | 11.4 KB | Display | FSC data file |
Images | emd_12604.png | 135.7 KB | ||
Masks | emd_12604_msk_1.map | 125 MB | Mask map | |
Filedesc metadata | emd-12604.cif.gz | 5.8 KB | ||
Others | emd_12604_additional_1.map.gz emd_12604_half_map_1.map.gz emd_12604_half_map_2.map.gz | 62.6 MB 116.1 MB 116.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-12604 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-12604 | HTTPS FTP |
-Validation report
Summary document | emd_12604_validation.pdf.gz | 1.1 MB | Display | EMDB validaton report |
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Full document | emd_12604_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | emd_12604_validation.xml.gz | 18.7 KB | Display | |
Data in CIF | emd_12604_validation.cif.gz | 24.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-12604 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-12604 | HTTPS FTP |
-Related structure data
Related structure data | 7nvhMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_12604.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | sharpened map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.832 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_12604_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: unsharpened map
File | emd_12604_additional_1.map | ||||||||||||
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Annotation | unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map B
File | emd_12604_half_map_1.map | ||||||||||||
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Annotation | half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map A
File | emd_12604_half_map_2.map | ||||||||||||
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Annotation | half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Mycolic acid transporter MmpL3
Entire | Name: Mycolic acid transporter MmpL3 |
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Components |
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-Supramolecule #1: Mycolic acid transporter MmpL3
Supramolecule | Name: Mycolic acid transporter MmpL3 / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Mycobacterium tuberculosis (bacteria) |
-Macromolecule #1: Trehalose monomycolate exporter MmpL3
Macromolecule | Name: Trehalose monomycolate exporter MmpL3 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mycobacterium tuberculosis (bacteria) |
Molecular weight | Theoretical: 82.525609 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MFAWWGRTVY RYRFIVIGVM VALCLGGGVF GLSLGKHVTQ SGFYDDGSQS VQASVLGDQV YGRDRSGHIV AIFQAPAGKT VDDPAWSKK VVDELNRFQQ DHPDQVLGWA GYLRASQATG MATADKKYTF VSIPLKGDDD DTILNNYKAI APDLQRLDGG T VKLAGLQP ...String: MFAWWGRTVY RYRFIVIGVM VALCLGGGVF GLSLGKHVTQ SGFYDDGSQS VQASVLGDQV YGRDRSGHIV AIFQAPAGKT VDDPAWSKK VVDELNRFQQ DHPDQVLGWA GYLRASQATG MATADKKYTF VSIPLKGDDD DTILNNYKAI APDLQRLDGG T VKLAGLQP VAEALTGTIA TDQRRMEVLA LPLVAVVLFF VFGGVIAAGL PVMVGGLCIA GALGIMRFLA IFGPVHYFAQ PV VSLIGLG IAIDYGLFIV SRFREEIAEG YDTETAVRRT VITAGRTVTF SAVLIVASAI GLLLFPQGFL KSLTYATIAS VML SAILSI TVLPACLGIL GKHVDALGVR TLFRVPFLAN WKISAAYLNW LADRLQRTKT REEVEAGFWG KLVNRVMKRP VLFA APIVI IMILLIIPVG KLSLGGISEK YLPPTNSVRQ AQEEFDKLFP GYRTNPLTLV IQTSNHQPVT DAQIADIRSK AMAIG GFIE PDNDPANMWQ ERAYAVGASK DPSVRVLQNG LINPADASKK LTELRAITPP KGITVLVGGT PALELDSIHG LFAKMP LMV VILLTTTIVL MFLAFGSVVL PIKATLMSAL TLGSTMGILT WIFVDGHFSK WLNFTPTPLT APVIGLIIAL VFGLSTD YE VFLVSRMVEA RERGMSTQEA IRIGTAATGR IITAAALIVA VVAGAFVFSD LVMMKYLAFG LMAALLLDAT VVRMFLVP S VMKLLGDDCW WAPRWARRLQ TRIGLGEIHL PDGSENLYFQ UniProtKB: Trehalose monomycolate exporter MmpL3 |
-Macromolecule #2: Lauryl Maltose Neopentyl Glycol
Macromolecule | Name: Lauryl Maltose Neopentyl Glycol / type: ligand / ID: 2 / Number of copies: 1 / Formula: AV0 |
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Molecular weight | Theoretical: 1.005188 KDa |
Chemical component information | ChemComp-AV0: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 2 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 58.2 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |