1ESZ

STRUCTURE OF THE PERIPLASMIC FERRIC SIDEROPHORE BINDING PROTEIN FHUD COMPLEXED WITH COPROGEN


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.241 
  • R-Value Work: 0.219 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

X-ray crystallographic structures of the Escherichia coli periplasmic protein FhuD bound to hydroxamate-type siderophores and the antibiotic albomycin.

Clarke, T.E.Braun, V.Winkelmann, G.Tari, L.W.Vogel, H.J.

(2002) J Biol Chem 277: 13966-13972

  • DOI: https://doi.org/10.1074/jbc.M109385200
  • Primary Citation of Related Structures:  
    1ESZ, 1K2V, 1K7S

  • PubMed Abstract: 

    Siderophore-binding proteins play an essential role in the uptake of iron in many Gram-positive and Gram-negative bacteria. FhuD is an ATP-binding cassette-type (ABC-type) binding protein involved in the uptake of hydroxamate-type siderophores in Escherichia coli. Structures of FhuD complexed with the antibiotic albomycin, the fungal siderophore coprogen and the drug Desferal have been determined at high resolution by x-ray crystallography. FhuD has an unusual bilobal structure for a periplasmic ligand binding protein, with two mixed beta/alpha domains connected by a long alpha-helix. The binding site for hydroxamate-type ligands is composed of a shallow pocket that lies between these two domains. Recognition of siderophores primarily occurs through interactions between the iron-hydroxamate centers of each siderophore and the side chains of several key residues in the binding pocket. Rearrangements of side chains within the binding pocket accommodate the unique structural features of each siderophore. The backbones of the siderophores are not involved in any direct interactions with the protein, demonstrating how siderophores with considerable chemical and structural diversity can be bound by FhuD. For albomycin, which consists of an antibiotic group attached to a hydroxamate siderophore, electron density for the antibiotic portion was not observed. Therefore, this study provides a basis for the rational design of novel bacteriostatic agents, in the form of siderophore-antibiotic conjugates that can act as "Trojan horses," using the hydroxamate-type siderophore uptake system to actively deliver antibiotics directly into targeted pathogens.


  • Organizational Affiliation

    Structural Biology Research Group, Department of Biological Sciences, University of Calgary, 2500 University Dr. N.W., Calgary, Alberta T2N 1N4, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
FERRICHROME-BINDING PERIPLASMIC PROTEIN266Escherichia coliMutation(s): 0 
UniProt
Find proteins for P07822 (Escherichia coli (strain K12))
Explore P07822 
Go to UniProtKB:  P07822
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP07822
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CPO
Query on CPO

Download Ideal Coordinates CCD File 
B [auth A]COPROGEN
C35 H53 Fe N6 O13
FQIVLXIUJLOKPL-FMHWUFKWSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
CPO Binding MOAD:  1ESZ Kd: 300 (nM) from 1 assay(s)
PDBBind:  1ESZ Kd: 300 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.241 
  • R-Value Work: 0.219 
  • Space Group: P 63
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.09α = 90
b = 86.09β = 90
c = 91.94γ = 120
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-04-17
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-07
    Changes: Data collection, Database references, Derived calculations