5JR8

Disposal of Iron by a Mutant form of Siderocalin NGAL


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.181 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Disposal of iron by a mutant form of lipocalin 2.

Barasch, J.Hollmen, M.Deng, R.Hod, E.A.Rupert, P.B.Abergel, R.J.Allred, B.E.Xu, K.Darrah, S.F.Tekabe, Y.Perlstein, A.Wax, R.Bruck, E.Stauber, J.Corbin, K.A.Buchen, C.Slavkovich, V.Graziano, J.Spitalnik, S.L.Bao, G.Strong, R.K.Qiu, A.

(2016) Nat Commun 7: 12973-12973

  • DOI: https://doi.org/10.1038/ncomms12973
  • Primary Citation of Related Structures:  
    5JR8

  • PubMed Abstract: 

    Iron overload damages many organs. Unfortunately, therapeutic iron chelators also have undesired toxicity and may deliver iron to microbes. Here we show that a mutant form (K3Cys) of endogenous lipocalin 2 (LCN2) is filtered by the kidney but can bypass sites of megalin-dependent recapture, resulting in urinary excretion. Because K3Cys maintains recognition of its cognate ligand, the iron siderophore enterochelin, this protein can capture and transport iron even in the acidic conditions of urine. Mutant LCN2 strips iron from transferrin and citrate, and delivers it into the urine. In addition, it removes iron from iron overloaded mice, including models of acquired (iron-dextran or stored red blood cells) and primary (Hfe -/- ) iron overload. In each case, the mutants reduce redox activity typical of non-transferrin-bound iron. In summary, we present a non-toxic strategy for iron chelation and urinary elimination, based on manipulating an endogenous protein:siderophore:iron clearance pathway.


  • Organizational Affiliation

    Columbia University, Russ Berrie Medical Science Pavilion, 1150 Saint Nicholas Avenue, Rm 411, New York, New York 10032, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Neutrophil gelatinase-associated lipocalin
A, B
178Homo sapiensMutation(s): 0 
Gene Names: LCN2HNLNGAL
UniProt & NIH Common Fund Data Resources
Find proteins for P80188 (Homo sapiens)
Explore P80188 
Go to UniProtKB:  P80188
PHAROS:  P80188
GTEx:  ENSG00000148346 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP80188
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.181 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 138.97α = 90
b = 138.97β = 90
c = 64.87γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
iMOSFLMdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

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Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2016-09-28
    Type: Initial release
  • Version 1.1: 2016-11-16
    Changes: Database references
  • Version 1.2: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description