title: The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition.
abstract: 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.
authors.affiliation: Molecular and Cellular Biology Program, Fred Hutchinson Cancer Research Center, Box 357275, University of Washington, Seattle, WA 98105, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Goetz
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Holmes
authors.forename: Niels
authors.initials: N
authors.lastname: Borregaard
authors.forename: Martin E
authors.initials: ME
authors.lastname: Bluhm
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Raymond
authors.forename: Roland K
authors.initials: RK
authors.lastname: Strong
mesh_terms: D000209:Acute-Phase Proteins / Q000737:chemistry / Q000494:pharmacology*; D002352:Carrier Proteins / Q000737:chemistry / Q000494:pharmacology*; D002412:Cations; D004758:Enterobactin / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008024:Ligands; D000071068:Lipocalin-2; D054834:Lipocalins; D008958:Models, Molecular; D015513:Oncogene Proteins / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011518:Proto-Oncogene Proteins; D017262:Siderophores / Q000378:metabolism*; D013054:Spectrophotometry, Atomic; D013997:Time Factors
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D002412:Cations; C489506:LCN2 protein, human; D008024:Ligands; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D017262:Siderophores; D004758:Enterobactin; D007501:Iron