THE STRUCTURE OF HUMAN MITOCHONDRIAL MANGANESE SUPEROXIDE-DISMUTASE REVEALS A NOVEL TETRAMERIC INTERFACE OF 2 4-HELIX BUNDLES
THE STRUCTURE OF HUMAN MITOCHONDRIAL MANGANESE SUPEROXIDE-DISMUTASE REVEALS A NOVEL TETRAMERIC INTERFACE OF 2 4-HELIX BUNDLES
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DOI：
10.1016/0092-8674(92)90270-m
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发表时间：
1992-10-02
期刊：
影响因子：
64.5
通讯作者：
TAINER, JA
中科院分区：
文献类型：
--
作者：
BORGSTAHL, GEO;PARGE, HE;TAINER, JA
已测定重组人锰超氧化物歧化酶（一种保护线粒体免受氧介导的自由基损伤的同型四聚体酶）2.2埃分辨率的晶体结构。在每个亚基内，N末端螺旋发夹结构和C末端α/β结构域都为催化性锰位点提供配体。两个相同的4 - 螺旋束由N末端螺旋发夹对称组装而成，形成新的四聚体界面，稳定活性位点。活性降低的结构改变的多态性变体，例如四聚体界面突变体Ile - 58变为Thr，可能不仅通过增强肿瘤坏死因子对病毒感染细胞的细胞毒性产生早期选择性优势，而且还会因线粒体氧化损伤增加而产生有害影响，从而导致退行性疾病，包括糖尿病、衰老以及帕金森病和阿尔茨海默病。
The 2.2 angstrom resolution crystal structure of recombinant human manganese superoxide dismutase, a homotetrameric enzyme that protects mitochondria against oxygen-mediated free radical damage, has been determined. Within each subunit, both the N-terminal helical hairpin and C-terminal alpha/beta domains contribute ligands to the catalytic manganese site. Two identical 4-helix bundles, symmetrically assembled from the N-terminal helical hairpins, form novel tetrameric interfaces that stabilize the active sites. Structurally altered polymorphic variants with reduced activity, such as tetrameric interface mutant Ile-58 to Thr, may produce not only an early selective advantage, through enhanced cytotoxicity of tumor necrosis factor for virus-infected cells, but also detrimental effects from increased mitochondrial oxidative damage, contributing to degenerative conditions, including diabetes, aging, and Parkinson's and Alzheimer's diseases.