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Yorodumi- PDB-7wnx: Cryo-EM structure of Mycobacterium smegmatis MmpL3 complexed with... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7wnx | |||||||||||||||
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Title | Cryo-EM structure of Mycobacterium smegmatis MmpL3 complexed with ST004 in lipid nanodiscs | |||||||||||||||
Components | Trehalose monomycolate exporter MmpL3 | |||||||||||||||
Keywords | MEMBRANE PROTEIN / drug target / novel compound / Mycobacterium tuberculosis | |||||||||||||||
Function / homology | Function and homology information phosphatidylethanolamine transfer activity / phosphatidylglycerol binding / trehalose transmembrane transporter activity / trehalose transport / mycolate cell wall layer assembly / diacylglycerol binding / cell wall biogenesis / cell pole / cell tip / mycolic acid biosynthetic process ...phosphatidylethanolamine transfer activity / phosphatidylglycerol binding / trehalose transmembrane transporter activity / trehalose transport / mycolate cell wall layer assembly / diacylglycerol binding / cell wall biogenesis / cell pole / cell tip / mycolic acid biosynthetic process / cardiolipin binding / cell septum / phospholipid transport / phosphatidylethanolamine binding / phosphatidylinositol binding / regulation of membrane potential / cell wall organization / response to xenobiotic stimulus / response to antibiotic / plasma membrane Similarity search - Function | |||||||||||||||
Biological species | Mycolicibacterium smegmatis MC2 155 (bacteria) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.36 Å | |||||||||||||||
Authors | Zhang, B. / Hu, T. / Yang, X. / Liu, F. / Rao, Z. | |||||||||||||||
Funding support | China, 4items
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Citation | Journal: Structure / Year: 2022 Title: Structure-based design of anti-mycobacterial drug leads that target the mycolic acid transporter MmpL3. Authors: Tianyu Hu / Xiaolin Yang / Fengjiang Liu / Shan Sun / Zhiqi Xiong / Jingxi Liang / Xiaobao Yang / Haofeng Wang / Xiuna Yang / Luke W Guddat / Haitao Yang / Zihe Rao / Bing Zhang / Abstract: New anti-tubercular agents are urgently needed to address the emerging threat of drug resistance to human tuberculosis. Here, we have used structure-assisted methods to develop compounds that target ...New anti-tubercular agents are urgently needed to address the emerging threat of drug resistance to human tuberculosis. Here, we have used structure-assisted methods to develop compounds that target mycobacterial membrane protein large 3 (MmpL3). MmpL3 is essential for the transport of mycolic acids, an important cell-wall component of mycobacteria. We prepared compounds that potently inhibit the growth of Mycobacterium tuberculosis (Mtb) and other mycobacteria in cell culture. The cryoelectron microscopy (cryo-EM) structure of mycobacterial MmpL3 in complex with one of these compounds (ST004) was determined using lipid nanodiscs at an overall resolution of 3.36 Å. The structure reveals the binding mode of ST004 to MmpL3, with the S4 and S5 subsites of the inhibitor-binding pocket in the proton translocation channel playing vital roles. These data are a promising starting point for the development of anti-tuberculosis drugs that target MmpL3. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7wnx.cif.gz | 186 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7wnx.ent.gz | 133.9 KB | Display | PDB format |
PDBx/mmJSON format | 7wnx.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7wnx_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 7wnx_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 7wnx_validation.xml.gz | 26.3 KB | Display | |
Data in CIF | 7wnx_validation.cif.gz | 38.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wn/7wnx ftp://data.pdbj.org/pub/pdb/validation_reports/wn/7wnx | HTTPS FTP |
-Related structure data
Related structure data | 32634MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 110056.781 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mycolicibacterium smegmatis MC2 155 (bacteria) Strain: MC2 155 / Gene: mmpL3 Production host: Mycolicibacterium smegmatis MC2 155 (bacteria) References: UniProt: A0QP27 |
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#2: Chemical | ChemComp-1I2 / |
Has ligand of interest | Y |
-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: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Mycolicibacterium smegmatis MC2 155 (bacteria) |
Source (recombinant) | Organism: Mycolicibacterium smegmatis MC2 155 (bacteria) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Microscopy | Model: FEI TITAN |
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Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.36 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 352885 / Symmetry type: POINT |