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

The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition
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DOI:
10.1016/s1097-2765(02)00708-6
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发表时间:
2002-11-01
期刊:
影响因子:
16
通讯作者:
Strong, RK
Strong, RK
中科院分区:
生物学1区
文献类型:
--
作者:
Goetz, DH;Holmes, MA;Strong, RK

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中性粒细胞明胶酶相关脂质运载蛋白(NGAL;也称为人中性粒细胞脂质运载蛋白、24p3、子宫脂质运载蛋白或神经相关脂质运载蛋白)最初被鉴定为中性粒细胞颗粒成分,是结合蛋白脂质运载蛋白家族的成员。包括中性粒细胞趋化因子(如N -甲酰化三肽)在内的假定的NGAL配体,都已被近期的生化和结构研究结果所否定。随后发现NGAL与多种细胞过程有关,但由于没有特征明确的配体,这些功能的分子基础仍然不清楚。在此我们报道,NGAL通过一种循环排列的、静电/阳离子 - π混合相互作用紧密结合细菌儿茶酚型铁载体,并且在铁限制条件下是一种有效的抑菌剂。因此我们提出,NGAL参与了先天免疫系统的抗菌铁耗竭策略。
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.