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Yorodumi- PDB-7nvh: Cryo-EM structure of the mycolic acid transporter MmpL3 from M. t... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7nvh | |||||||||||||||||||||
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Title | Cryo-EM structure of the mycolic acid transporter MmpL3 from M. tuberculosis | |||||||||||||||||||||
Components | Trehalose monomycolate exporter MmpL3 | |||||||||||||||||||||
Keywords | MEMBRANE PROTEIN / TRANSPORTER | |||||||||||||||||||||
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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | |||||||||||||||||||||
Authors | Adams, O. / Deme, J.C. / Parker, J.L. / Lea, S.M. / Newstead, S. | |||||||||||||||||||||
Funding support | United Kingdom, 6items
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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 | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7nvh.cif.gz | 134.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7nvh.ent.gz | 102.2 KB | Display | PDB format |
PDBx/mmJSON format | 7nvh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7nvh_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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Full document | 7nvh_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 7nvh_validation.xml.gz | 38 KB | Display | |
Data in CIF | 7nvh_validation.cif.gz | 54.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nv/7nvh ftp://data.pdbj.org/pub/pdb/validation_reports/nv/7nvh | HTTPS FTP |
-Related structure data
Related structure data | 12604MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 82525.609 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mycobacterium tuberculosis (bacteria) / Gene: mmpL3, Rv0206c, MTCY08D5.01c, MTV033.14c / Production host: Escherichia coli (E. coli) / References: UniProt: P9WJV5, UniProt: A0A658HT16*PLUS |
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#2: Chemical | ChemComp-AV0 / |
Has ligand of interest | N |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Mycolic acid transporter MmpL3 / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Mycobacterium tuberculosis (bacteria) |
Source (recombinant) | Organism: Escherichia coli (E. coli) |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 58.2 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 414082 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Highest resolution: 3 Å | ||||||||||||||||||||||||
Refine LS restraints |
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