3FW4

Crystal structure of Siderocalin (NGAL, Lipocalin 2) complexed with Ferric Catechol

3FW4 の概要

• エントリーDOI: 10.2210/pdb3fw4/pdb
• 関連するPDBエントリー: 3FW5
• 分子名称: Neutrophil gelatinase-associated lipocalin, FE (III) ION, CATECHOL, ... (7 entities in total)
• 機能のキーワード: 8-stranded anti-parallel beta barrel, 310-helix, glycoprotein, pyrrolidone carboxylic acid, secreted, transport protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P80188
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 63491.67

構造登録者

Clifton, M.C.,Strong, R.K. (登録日: 2009-01-16, 公開日: 2010-05-05, 最終更新日: 2024-10-16)

主引用文献

Bao, G.,Clifton, M.,Hoette, T.M.,Mori, K.,Deng, S.X.,Qiu, A.,Viltard, M.,Williams, D.,Paragas, N.,Leete, T.,Kulkarni, R.,Li, X.,Lee, B.,Kalandadze, A.,Ratner, A.J.,Pizarro, J.C.,Schmidt-Ott, K.M.,Landry, D.W.,Raymond, K.N.,Strong, R.K.,Barasch, J.
Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex.
Nat.Chem.Biol., 6:602-609, 2010

PubMed Abstract: The lipocalins are secreted proteins that bind small organic molecules. Scn-Ngal (also known as neutrophil gelatinase associated lipocalin, siderocalin, lipocalin 2) sequesters bacterial iron chelators, called siderophores, and consequently blocks bacterial growth. However, Scn-Ngal is also prominently expressed in aseptic diseases, implying that it binds additional ligands and serves additional functions. Using chemical screens, crystallography and fluorescence methods, we report that Scn-Ngal binds iron together with a small metabolic product called catechol. The formation of the complex blocked the reactivity of iron and permitted its transport once introduced into circulation in vivo. Scn-Ngal then recycled its iron in endosomes by a pH-sensitive mechanism. As catechols derive from bacterial and mammalian metabolism of dietary compounds, the Scn-Ngal-catechol-Fe(III) complex represents an unforeseen microbial-host interaction, which mimics Scn-Ngal-siderophore interactions but instead traffics iron in aseptic tissues. These results identify an endogenous siderophore, which may link the disparate roles of Scn-Ngal in different diseases.

PubMed: 20581821
DOI: 10.1038/nchembio.402

実験手法

X-RAY DIFFRACTION (2.3 Å)