Biochemical characterization and ligand binding properties of neuroglobin, a novel member of the globin family

被引:407
作者
Dewilde, S
Kiger, L
Burmester, T
Hankeln, T
Baudin-Creuza, V
Aerts, T
Marden, MC
Caubergs, R
Moens, L
机构
[1] Univ Instelling Antwerp, Dept Biochem, B-2610 Antwerp, Belgium
[2] Hop Bicetre, INSERM, F-94275 Le Kremlin Bicetre, France
[3] Johannes Gutenberg Univ Mainz, Inst Zool, D-55099 Mainz, Germany
[4] Johannes Gutenberg Univ Mainz, Inst Mol Genet Biosafety Res & Consulting, D-55099 Mainz, Germany
[5] Univ Instelling Antwerp, Dept Biol, B-2610 Antwerp, Belgium
关键词
D O I
10.1074/jbc.M106438200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Neuroglobin is a recently discovered member of the globin superfamily that is suggested to enhance the O-2 supply of the vertebrate brain. Spectral measurements with human and mouse recombinant neuroglobin provide evidence for a hexacoordinated deoxy ferrous (Fe2+) form, indicating a His-Fe2+-His binding scheme. O-2 or CO can displace the endogenous protein ligand, which is identified as the distal histidine by mutagenesis. The ferric (Fe3+) form of neuroglobin is also hexacoordinated with the protein ligand E7-His and does not exhibit pH dependence. Flash photolysis studies show a high recombination rate (k(on)) and a slow dissociation rate (k(off)) for both O-2 and CO, indicating a high intrinsic affinity for these ligands. However, because the rate-limiting step in ligand combination with the deoxy hexacoordinated form involves the dissociation of the protein ligand, O-2 and CO binding is suggested to be slow in vivo. Because of this competition, the observed O-2 affinity of recombinant human neuroglobin is average (1 torr at 37 degrees C). Neuroglobin has a high autoxidation rate, resulting in an oxidation at 37 degrees C by air within a few minutes. The oxidation/reduction potential of mouse neuroglobin (E'(o) = -129 mV) lies within the physiological range. Under natural conditions, recombinant mouse neuroglobin occurs as a monomer with disulfide-dependent formation of dimers. The biochemical and kinetic characteristics are discussed in view of the possible functions of neuroglobin in the vertebrate brain.
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页码:38949 / 38955
页数:7
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