大鼠铜蓝蛋白：一个新的不稳定铜结合位点和锌/铜镶嵌结构。

Rat ceruloplasmin: a new labile copper binding site and zinc/copper mosaic.

机构信息

Shubnikov Institute of Crystallography of FSRC "Crystallography and Photonics" RAS, Leninsky pr.59, Moscow 117333, Russia.

Institute of Experimental Medicine, ul. Academica Pavlova, 12, Saint-Petersburg 197376, Russia and Saint-Petersburg State Universisty, Universitetskaya nab. 7-9, Saint-Petersburg 199034, Russia and Centre of Preclinical Translational Research, Almazov National Medical Research Centre, ul. Dolgoozernaya, 43, Saint-Petersburg 197371, Russia.

出版信息

Metallomics. 2017 Dec 1;9(12):1828-1838. doi: 10.1039/c7mt00157f. Epub 2017 Nov 27.

DOI:10.1039/c7mt00157f

PMID:29177316

Abstract

Ceruloplasmin (Cp) is a copper-containing multifunctional oxidase of plasma, an antioxidant, an acute-phase protein and a free radical scavenger. The structural organization of Cp causes its sensitivity to proteolysis and ROS (reactive oxygen species), which can alter some of the important Cp functions. Elucidation of the orthorhombic crystal structure of rat Cp at 2.3 Å resolution revealed the basis for stronger resistance of rat Cp to proteolysis and a new labile copper binding site. The presence of this site appears as a very rare and distinctive feature of rat Cp as was shown by sequence alignment of ceruloplasmin, hephaestin and zyklopen in the Deuterostomia taxonomic group. The trigonal crystal form of rat Cp at 3.2 Å demonstrates unexpected partial substitution of copper by zinc.

摘要

铜蓝蛋白（Cp）是一种含铜的多功能血浆氧化酶，具有抗氧化、急性期蛋白和自由基清除剂的功能。Cp 的结构组织使其对蛋白水解和 ROS（活性氧）敏感，这可能会改变其一些重要的功能。通过解析分辨率为 2.3 Å 的大鼠 Cp 的正交晶体结构，揭示了大鼠 Cp 对蛋白水解具有更强抵抗力的基础，以及一个新的不稳定铜结合位点。该位点的存在似乎是大鼠 Cp 的一个非常罕见和独特的特征，这在 Deuterostomia 分类群的铜蓝蛋白、赫菲斯塔斯蛋白和泽克洛平的序列比对中得到了证实。大鼠 Cp 的三角晶体形式在 3.2 Å 处显示出锌对铜的意外部分取代。