The structure of murine neuroglobin: Novel pathways for ligand migration and binding
The structure of murine neuroglobin: Novel pathways for ligand migration and binding
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DOI：
10.1002/prot.20113
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发表时间：
2004-07-01
影响因子：
2.9
通讯作者：
Nienhaus, GU
中科院分区：
文献类型：
--
作者：
Vallone, B;Nienhaus, K;Nienhaus, GU
脑红蛋白是最近发现的一种珠蛋白，主要在脊椎动物的神经元组织中表达，它在血红素铁的第六配位结合了小的气态配体。在没有外源配体的情况下，远端组氨酸(His64)在亚铁和亚铁状态下与血红素铁结合。小鼠铁(MET)脑红蛋白在1.5埃的晶体结构揭示了与配体结合机制相关的有趣特征。对于两种可能的血红素取向，只观察到很弱的选择性，占位比为70：30。在血红素远端有两个小的内腔。这使得His64(E7)侧链在外源配体结合时能够移开。此外，连接血红素两侧的第三个巨大的空腔(体积约为290埃(3))向外开放，为配体提供了一个潜在的通道。CD和EF角显示出相当大的灵活性，这可能有助于配体进入蛋白质并访问活性部位。基于这种高分辨率结构，可以计划进行进一步的结构-功能研究，以阐明脑红蛋白在低氧生理反应中的作用。(C)2004年Wiley-Liss公司
Neuroglobin, a recently discovered globin predominantly expressed in neuronal tissue of vertebrates, binds small, gaseous ligands at the sixth coordination position of the heme iron. In the absence of an exogenous ligand, the distal histidine (His64) binds to the heme iron in the ferrous and ferric states. The crystal structure of murine ferric (met) neuroglobin at 1.5 Angstrom reveals interesting features relevant to the ligand binding mechanism. Only weak selectivity is observed for the two possible heme orientations, the occupancy ratio being 70:30. Two small internal cavities are present on the heme distal. side, which enable the His64(E7) side chain to move out of the way upon exogenous ligand binding. Moreover, a third, huge cavity (volume approximately 290 Angstrom(3)) connecting both sides of the heme, is open towards the exterior and provides a potential passageway for ligands. The CD and EF corners exhibit substantial flexibility, which may assist ligands in entering the protein and accessing the active site. Based on this high-resolution structure, further structure-function studies can be planned to elucidate the role of neuroglobin in physiological responses to hypoxia. (C) 2004 Wiley-Liss, Inc.