The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition

Mol Cell. 2002 Nov;10(5):1033-43. doi: 10.1016/s1097-2765(02)00708-6.


First identified as a neutrophil granule component, neutrophil gelatinase-associated lipocalin (NGAL; also called human neutrophil lipocalin, 24p3, uterocalin, or neu-related lipocalin) is a member of the lipocalin family of binding proteins. Putative NGAL ligands, including neutrophil chemotactic agents such as N-formylated tripeptides, have all been refuted by recent biochemical and structural results. NGAL has subsequently been implicated in diverse cellular processes, but without a characterized ligand, the molecular basis of these functions remained mysterious. Here we report that NGAL tightly binds bacterial catecholate-type ferric siderophores through a cyclically permuted, hybrid electrostatic/cation-pi interaction and is a potent bacteriostatic agent in iron-limiting conditions. We therefore propose that NGAL participates in the antibacterial iron depletion strategy of the innate immune system.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute-Phase Proteins / chemistry
  • Acute-Phase Proteins / pharmacology*
  • Carrier Proteins / chemistry
  • Carrier Proteins / pharmacology*
  • Cations
  • Enterobactin / metabolism
  • Escherichia coli / metabolism
  • Iron / metabolism*
  • Ligands
  • Lipocalin-2
  • Lipocalins
  • Models, Molecular
  • Oncogene Proteins / chemistry
  • Oncogene Proteins / pharmacology*
  • Protein Binding
  • Proto-Oncogene Proteins
  • Siderophores / metabolism*
  • Spectrophotometry, Atomic
  • Time Factors


  • Acute-Phase Proteins
  • Carrier Proteins
  • Cations
  • LCN2 protein, human
  • Ligands
  • Lipocalin-2
  • Lipocalins
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • Siderophores
  • Enterobactin
  • Iron

Associated data

  • PDB/1L6M