[English] 日本語
Yorodumi
- PDB-7nvh: Cryo-EM structure of the mycolic acid transporter MmpL3 from M. t... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7nvh
TitleCryo-EM structure of the mycolic acid transporter MmpL3 from M. tuberculosis
ComponentsTrehalose monomycolate exporter MmpL3
KeywordsMEMBRANE PROTEIN / TRANSPORTER
Function / homology
Function and homology information


phosphatidylglycerol binding / Actinobacterium-type cell wall biogenesis / diacylglycerol binding / lipopolysaccharide transport / cell tip / mycolic acid biosynthetic process / cardiolipin binding / cell septum / phosphatidylethanolamine binding / regulation of membrane potential ...phosphatidylglycerol binding / Actinobacterium-type cell wall biogenesis / diacylglycerol binding / lipopolysaccharide transport / cell tip / mycolic acid biosynthetic process / cardiolipin binding / cell septum / phosphatidylethanolamine binding / regulation of membrane potential / phosphatidylinositol binding / peptidoglycan-based cell wall / cell wall organization / membrane => GO:0016020 / response to antibiotic / plasma membrane
Similarity search - Function
Membrane transport protein MMPL domain / MMPL family / Sterol-sensing domain (SSD) profile. / Sterol-sensing domain
Similarity search - Domain/homology
Lauryl Maltose Neopentyl Glycol / Trehalose monomycolate RND transporter MmpL3 / Trehalose monomycolate exporter MmpL3
Similarity search - Component
Biological speciesMycobacterium tuberculosis (bacteria)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å
AuthorsAdams, O. / Deme, J.C. / Parker, J.L. / Lea, S.M. / Newstead, S.
Funding support United Kingdom, 6items
OrganizationGrant numberCountry
Wellcome Trust201536 United Kingdom
Wellcome Trust215519 United Kingdom
Wellcome Trust219531 United Kingdom
Medical Research Council (MRC, United Kingdom)MR/S021043/1 United Kingdom
Medical Research Council (MRC, United Kingdom)S021264 United Kingdom
Biotechnology and Biological Sciences Research Council (BBSRC)BB/M011224/1 United Kingdom
CitationJournal: 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
DepositionMar 15, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 16, 2021Provider: repository / Type: Initial release
Revision 1.1Jul 21, 2021Group: Database references / Category: citation / citation_author
Item: _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Oct 20, 2021Group: Data collection / Database references
Category: citation / database_2 ...citation / database_2 / em_admin / pdbx_database_proc
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _em_admin.last_update
Revision 1.3Dec 21, 2022Group: Database references / Source and taxonomy / Structure summary
Category: citation / entity ...citation / entity / entity_name_com / entity_src_gen / struct_ref / struct_ref_seq / struct_ref_seq_dif
Item: _citation.page_last / _entity.pdbx_description ..._citation.page_last / _entity.pdbx_description / _entity_src_gen.pdbx_gene_src_gene / _struct_ref.db_code / _struct_ref.pdbx_db_accession / _struct_ref_seq.pdbx_db_accession / _struct_ref_seq_dif.pdbx_seq_db_accession_code

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Simplified surface model + fitted atomic model
  • EMDB-12604
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-12604
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Trehalose monomycolate exporter MmpL3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)83,5312
Polymers82,5261
Non-polymers1,0051
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area0 Å2
ΔGint0 kcal/mol
Surface area29260 Å2

-
Components

#1: Protein Trehalose monomycolate exporter MmpL3 / TMM exporter MmpL3 / MmpL3 transporter / Mycobacterial membrane protein large 3


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
#2: Chemical ChemComp-AV0 / 2-decyl-2-{[(4-O-alpha-D-glucopyranosyl-beta-D-glucopyranosyl)oxy]methyl}dodecyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside / 2,2-didecylpropane-1,3-bis-b-D-maltopyranoside


Mass: 1005.188 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C47H88O22
Has ligand of interestN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: Mycolic acid transporter MmpL3 / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / Source: RECOMBINANT
Source (natural)Organism: Mycobacterium tuberculosis (bacteria)
Source (recombinant)Organism: Escherichia coli (E. coli)
Buffer solutionpH: 7.5
SpecimenConc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy
Image recordingElectron dose: 58.2 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

-
Processing

SoftwareName: PHENIX / Version: 1.18.2_3874: / Classification: refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 414082 / Symmetry type: POINT
RefinementHighest resolution: 3.02 Å
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0045650
ELECTRON MICROSCOPYf_angle_d0.617693
ELECTRON MICROSCOPYf_dihedral_angle_d12.726801
ELECTRON MICROSCOPYf_chiral_restr0.044930
ELECTRON MICROSCOPYf_plane_restr0.005950

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more