Ligand Preference Inferred from the Structure of Neutrophil Gelatinase Associated Lipocalin

Citations Over Time

Abstract

Neutrophil gelatinase associated lipocalin (NGAL), a constituent of neutrophil granules, is a member of the lipocalin family of binding proteins. NGAL can also be highly induced in epithelial cells in both inflammatory and neoplastic colorectal disease. NGAL is proposed to mediate inflammatory responses by sequestering neutrophil chemoattractants, particularly N-formylated tripeptides and possibly leukotriene B(4) and platelet activating factor. The crystal structures of NGAL display a typical lipocalin fold, albeit with an unusually large and atypically polar binding site, or calyx. The fold of NGAL is most similar to the epididymal retinoic acid-binding protein, another lipocalin, though the overall architecture of the calyces are very different. The crystal structures also reveal either sulfate ions or an adventitiously copurified fatty acid bound in the binding site. Neither ligand is displaced by added N-formylated tripeptides. The size, shape, and character of the NGAL calyx, as well as the low relative affinity for N-formylated tripeptides, suggest that neither the copurified fatty acid nor any of the proposed ligands are likely to be the preferred ligand of this protein. Comparisons between the crystal structures and the recently reported solution structure of NGAL reveal significant differences, in terms of both the details of the structure and the overall flexibility of the fold.

Related Papers

• → High expression of neutrophil gelatinase-associated lipocalin (NGAL) in the kidney proximal tubules of diabetic rats(2015)36 cited
• → Correction: Cinnamtannin A2 protects the renal injury by attenuates the altered expression of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) expression in 5/6 nephrectomized rat model(2023)1 cited
• → NGAL : neutrophil gelatinase-associated lipocalin, siderocalin, lipocalin 2(2010)1 cited
• Iconographies supplémentaires de l'article : NGAL : neutrophil gelatinase-associated lipocalin, siderocalin, lipocalin 2(2010)
• 心臓血管手術・呼吸器外科手術術後バイオマーカーとしての Lipocalin-2/neutrophil gelatinase-associated lipocalin の検討(2011)