The heme environment of mouse neuroglobin - Evidence for the presence of two conformations of the heme pocket
The heme environment of mouse neuroglobin - Evidence for the presence of two conformations of the heme pocket
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DOI：
10.1074/jbc.m103907200
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发表时间：
2001-09-28
影响因子：
4.8
通讯作者：
Rousseau, DL
中科院分区：
文献类型：
--
作者：
Couture, M;Burmester, T;Rousseau, DL
神经球蛋白（Neuroglobin, Ngb）是一种新发现的氧结合血红素蛋白，主要在人类和其他脊椎动物的大脑中表达。为了表征这种新的血红素蛋白的结构/功能关系，我们利用共振拉曼光谱测定了小鼠Ngb中血红素环境的结构。在Fe2+CO配合物中，存在两种Fe-CO单元构象，其中一种来自血红素口袋的开放构象，其中CO不与附近的任何残基相互作用，另一种来自封闭构象，其中CO基团附近的带正电的残基稳定了配合物。对于Fe2+O2复合物，我们检测到一个单一的upsilon （Fe-OO）拉伸模式，其频率与脊椎动物的氧肌红蛋白和氧血红蛋白相似（571 cm(-1)）。基于Ngb封闭构象的Fe-C-O频率，我们预测在一个极远环境下，Ngb的O-2 off率低于Mb的off率。在没有外源配体的情况下，血红素袋残基与血红素铁结合，形成一个六坐标配合物，从而预测外源配体的on率较低。讨论了Ngb血红素口袋的这些结构特性及其在体内的氧传递功能。
Neuroglobin (Ngb) is a newly discovered oxygen-binding heme protein that is primarily expressed in the brain of humans and other vertebrates. To characterize the structure/function relationships of this new heme protein, we have used resonance Raman spectroscopy to determine the structure of the heme environment in Ngb from mice. In the Fe2+CO complex, two conformations of the Fe-CO unit are present, one of which arises from an open conformation of the heme pocket in which the CO is not interacting with any nearby residue, and the other arises from a closed conformation where a positively charged residue near the CO group stabilizes the complex. For the Fe2+O2 complex, we detect a single upsilon (Fe-OO) stretching mode at a frequency similar to that of oxymyoglobins and oxyhemoglobins of vertebrates (571 cm(-1)). Based on the Fe-C-O frequencies of the closed conformation of Ngb, a highly polar distal environment is indicated from which the O-2 off-rate is predicted to be lower than that of Mb. In the absence of exogenous ligands, a heme pocket residue coordinates to the heme iron, forming a six-coordinate complex, thereby predicting a low on-rate for exogenous ligands. These structural properties of the heme pocket of Ngb are discussed with respect to its proposed in vivo oxygen delivery function.