Nickel superoxide dismutase structure and mechanism
Nickel superoxide dismutase structure and mechanism
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DOI：
10.1021/bi0496081
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发表时间：
2004-06-29
期刊：
影响因子：
2.9
通讯作者：
Getzoff, ED
中科院分区：
文献类型：
--
作者：
Barondeau, DP;Kassmann, CJ;Getzoff, ED
镍超氧化物歧化酶（NiSOD）的1.30埃分辨率晶体结构确定了一种新的SOD折叠，组装和Ni活性位点。NiSOD是一个六聚体组装的右手4-螺旋束的up-down-up-down拓扑结构与N-末端钩螯合的活性位点镍离子。这种新鉴定的九残基Ni钩结构基序（His-Cys-X-X-Pro-Cys-Gly-X-Tyr）提供了几乎所有对金属结合和催化至关重要的相互作用，因此可能是NiSOD的诊断。保守的赖氨酸残基被定位用于超氧阴离子到狭窄的活性位点通道的静电引导。载脂蛋白结构表明，镍钩基序是前金属结合展开。活性位点Ni几何形状从正方形平面Ni（II），与硫醇盐（Cys 2和Cys 6）和骨架氮（His 1和Cys 2）配体，到正方形金字塔Ni（III）与添加的轴向His 1侧链配体，与电子顺磁共振光谱一致。三个NiSOD的结构和比较的Cu，Zn和Mn/Fe SOD的分析支持特定的分子机制NiSOD的成熟和催化，并确定重要的结构-功能之间的关系保守的SOD。
The 1.30 Angstrom resolution crystal structure of nickel superoxide dismutase (NiSOD) identifies a novel SOD fold, assembly, and Ni active site. NiSOD is a hexameric assembly of right-handed 4-helix bundles of up-down-up-down topology with N-terminal hooks chelating the active site Ni ions. This newly identified nine-residue Ni-hook structural motif (His-Cys-X-X-Pro-Cys-Gly-X-Tyr) provides almost all interactions critical for metal binding and catalysis, and thus will likely be diagnostic of NiSODs. Conserved lysine residues are positioned for electrostatic guidance of the superoxide anion to the narrow active site channel. Apo structures show that the Ni-hook motif is unfolded prior to metal binding. The active site Ni geometry cycles from square planar Ni(II), with thiolate (Cys2 and Cys6) and backbone nitrogen (His1 and Cys2) ligands, to square pyramidal Ni(III) with an added axial His1 side chain ligand, consistent with electron paramagentic resonance spectroscopy. Analyses of the three NiSOD structures and comparisons to the Cu,Zn and Mn/Fe SODs support specific molecular mechanisms for NiSOD maturation and catalysis, and identify important structure-function relationships conserved among SODs.