Crystal structure of the human vascular adhesion protein-1: Unique structural features with functional implications
Crystal structure of the human vascular adhesion protein-1: Unique structural features with functional implications
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DOI：
10.1110/ps.051438105
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发表时间：
2005-08-01
期刊：
影响因子：
8
通讯作者：
Salminen, TA
中科院分区：
文献类型：
--
作者：
Airenne, TT;Nymalm, Y;Salminen, TA
人血管粘附蛋白-1（hVAP-1）的表达在发生淋巴细胞从血液外渗到外周组织的炎症部位被诱导。我们已经解决了人铜胺氧化酶（CAO）的X射线结构的hVAP-1，这是不同于其他CAO的膜结合。二聚体的结构揭示了一些有趣的功能，可能有基本的作用，在粘附和酶的功能的hVAP-1，特别是关于的作用，hVAP-1在炎症，淋巴细胞附着，和信号。首先，底物通道中的Leu 469可能在控制底物进入方面发挥关键作用;根据其构象，它可以阻止或提供进入活性位点的途径。其次，在六个预测的N-糖基化位点中的两个处清楚地观察到糖单元。此外，突变分析表明，所有预测的位点在用于结晶的蛋白质中被糖基化。第三，在hVAP-1中每个活性位点的入口处存在溶剂暴露的RGD基序，这表明它可能具有功能性作用。
The expression of human vascular adhesion protein-1 (hVAP-1) is induced at sites of inflammation where extravasation of lymphocytes from blood to the peripheral tissue occurs. We have solved the X-ray structure of hVAP-1, a human copper amine oxidase (CAO), which is distinguished from other CAOs in being membrane-bound. The dimer structure reveals some intriguing features that may have fundamental roles in the adhesive and enzymatic functions of hVAP-1, especially regarding the role of hVAP-1 in inflammation, lymphocyte attachment, and signaling. Firstly, Leu469 at the substrate channel may play a key role in controlling the substrate entry; depending on its conformation, it either blocks or gives access to the active site. Secondly, sugar units are clearly observed at two of the six predicted N-glycosylation sites. Moreover, mutagenesis analysis showed that all of the predicted sites were glycosylated in the protein used for crystallization. Thirdly, the existence of a solvent-exposed RGD motif at the entrance to each active site in hVAP-1 suggests that it may have a functional role.