The Structure of Human Extracellular Copper-Zinc Superoxide Dismutase at 1.7 Å Resolution: Insights into Heparin and Collagen Binding
The Structure of Human Extracellular Copper-Zinc Superoxide Dismutase at 1.7 Å Resolution: Insights into Heparin and Collagen Binding
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DOI：
10.1016/j.jmb.2009.03.026
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发表时间：
2009-05-01
影响因子：
5.6
通讯作者：
Hasnain, S. Samar
中科院分区：
文献类型：
--
作者：
Antonyuk, Svetlana V.;Strange, Richard W.;Hasnain, S. Samar
细胞外超氧化物歧化酶 (SOD3) 是一种同源四聚体含铜和锌的糖蛋白，对肝素具有亲和力。血管壁和肺部的 SOD3 水平特别高。该酶具有多种作用，包括保护肺部免受高氧血症和保存一氧化氮。常见突变 R213G 可降低 SOD3 的肝素亲和力，与心肌梗塞和中风风险增加相关。我们报告了人类 SOD3 的第一个晶体结构，分辨率为 1.7 埃。 SOD3 二聚体的整体亚基折叠和亚基-亚基界面与 Cu-Zn SOD (SOD1) 中的相应结构相似。金属结合位点与 SOD1 中发现的类似，但铜结合位点的 Asn180 取代了 Thr137，锌结合位点的环更短。二聚体形成功能性同四聚体，该同四聚体是通过每个亚基上两个延伸环之间的接触而形成的。四聚化和肝素结合所需的 N 端和 C 端区域分别具有高度灵活性。由四聚体界面形成的两个凹槽暗示了肝素和胶原蛋白结合的可能位点。 (C) 2009 Elsevier Ltd. 保留所有权利。
Extracellular superoxide dismutase (SOD3) is a homotetrameric copper-and zinc-containing glycoprotein with affinity for heparin. The level of SOD3 is particularly high in blood vessel walls and in the lungs. The enzyme has multiple roles including protection of the lungs against hyperoxia and preservation of nitric oxide. The common mutation R213G, which reduces the heparin affinity of SOD3, is associated with increased risk of myocardial infarctions and stroke. We report the first crystal structure of human SOD3 at 1.7 angstrom resolution. The overall subunit fold and the subunit-subunit interface of the SOD3 dimer are similar to the corresponding structures in Cu-Zn SOD (SOD1). The metal-binding sites are similar to those found in SOD1, but with Asn180 replacing Thr137 at the Cu-binding site and a much shorter loop at the zinc-binding site. The dimers form a functional homotetramer that is fashioned through contacts between two extended loops on each subunit. The N- and C-terminal end regions required for tetramerisation and heparin binding, respectively, are highly flexible. Two grooves fashioned by the tetramer interface are suggestive as the probable sites for heparin and collagen binding. (C) 2009 Elsevier Ltd. All rights reserved.