Related Experiment Video

Updated: May 21, 2025

Essential Metal Uptake in Gram-negative Bacteria: X-ray Fluorescence, Radioisotopes, and Cell Fractionation
10:34

Essential Metal Uptake in Gram-negative Bacteria: X-ray Fluorescence, Radioisotopes, and Cell Fractionation

Published on: February 1, 2018

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Molecular insights into ferric-siderophore transport by the putative TonB-dependent transporter in Mycobacterium

Gauri Shankar1, Yusuf Akhter1

  • 1Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, India.

Journal of Biomolecular Structure & Dynamics
|March 17, 2025
PubMed

Insights

Mycobacterium tuberculosis uses siderophores and FecA transporters to acquire iron. This study reveals how ferric-siderophore complexes move through FecA, offering insights into tuberculosis pathogenesis and potential new therapies.

Area of Science:

  • Microbiology
  • Structural Biology
  • Biophysics

Background:

  • Iron acquisition is crucial for Mycobacterium tuberculosis (Mtb) virulence.
  • Mtb utilizes high-affinity siderophores to scavenge iron from host cells.
  • TonB-dependent transporters, such as FecA, mediate siderophore-iron uptake.

Purpose of the Study:

  • To elucidate the molecular mechanisms of FecA-mediated ferric-siderophore transport in Mtb.
  • To understand the structural dynamics governing iron import into Mtb.
  • To identify potential therapeutic targets for disrupting Mtb iron acquisition.

Main Methods:

  • Molecular docking simulations to predict ligand-protein interactions.
  • Molecular dynamics simulations to analyze conformational changes.
  • Analysis of extracellular loops, outer membrane barrel, and plug domains.

Main Results:

  • Ferric-siderophore binding initiates at an extracellular pocket on FecA.
  • Ligand transport involves migration through a dynamic tunnel, expanding via conformational changes.
  • Induced fit model describes transport, with ligand interaction causing 2-10 Å shifts in FecA regions.
  • Precise positioning of extracellular loops is vital for efficient ligand binding and transport.

Conclusions:

  • FecA-mediated ferric-siderophore transport in Mtb follows an induced fit mechanism.
  • Conformational dynamics of FecA facilitate iron import into Mtb.
  • Understanding these iron uptake pathways can inform novel therapeutic strategies against tuberculosis.
Keywords:
FecAMycobacteriumironouter membrane proteinsiderophoretuberculosis

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