Ligand preference inferred from the structure of neutrophil gelatinase associated lipocalin
Ligand preference inferred from the structure of neutrophil gelatinase associated lipocalin
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DOI：
10.1021/bi992215v
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发表时间：
2000-02-29
期刊：
影响因子：
2.9
通讯作者：
Strong, RK
中科院分区：
文献类型：
--
作者：
Goetz, DH;Willie, ST;Strong, RK
中性粒细胞明胶酶相关脂质运载蛋白（NGAL）是中性粒细胞颗粒的组成部分，是结合蛋白脂质运载蛋白家族的成员。NGAL也可在炎性和肿瘤性结直肠疾病的上皮细胞中高度诱导。NGAL被认为通过隔离中性粒细胞化学引诱物，特别是N-甲酰化三肽和可能的白三烯B-4和血小板活化因子介导炎症反应。NGAL的晶体结构显示出典型的脂质运载蛋白折叠，尽管具有异常大的且具有极性的结合位点或花萼。NGAL的折叠与附睾视黄酸结合蛋白（另一种脂质运载蛋白）最相似，尽管肾盏的整体结构非常不同。晶体结构还揭示了硫酸根离子或在结合位点结合的偶然共纯化脂肪酸。两种配体都不被添加的N-甲酰化三肽取代。NGAL萼的大小、形状和特征，以及对N-甲酰化三肽的低相对亲和力，表明共纯化脂肪酸和任何提出的配体都不可能是该蛋白的优选配体。NGAL的晶体结构和最近报道的溶液结构之间的比较显示出显着的差异，在结构的细节和折叠的整体灵活性方面。
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.