Structure of the cytosolic Cu,Zn superoxide dismutase from Schistosoma mansoni
Structure of the cytosolic Cu,Zn superoxide dismutase from Schistosoma mansoni
复制标题
DOI：
10.1107/s0907444904016798
复制
发表时间：
2004-09-01
影响因子：
2.2
通讯作者：
Garratt, RC
中科院分区：
文献类型：
--
作者：
Cardoso, RMF;Silva, CHTP;Garratt, RC
铜锌超氧化物歧化酶（Cu，ZnSOD）是保护细胞免受活性氧毒害的必需酶。在人类中，两个不同的Cu，Zn SOD基因位于4号和21号染色体上，后者的突变与家族性肌萎缩侧索硬化症有关。类似地，寄生虫（吸虫寄生虫，负责慢性衰弱性疾病血吸虫病）也产生两种不同的铜，锌SOD，在这种情况下，一个胞质和一个轴承的信号肽。对人曼氏血吸虫（Schistosoma mansoni）的胞质形式的酶（SmCtSOD）的晶体结构进行了解析，并将其精确到2.2埃（空间群P2（1）2（1），R = 17.6%和R-free = 24.1%）和1.55埃（空间群P2（1），R = 15.7%和R-free = 17.1%）的分辨率。这是首次报道人寄生虫铜锌超氧化物歧化酶的晶体结构。替代位置的催化铜和它的水配体进行了改进的1.55埃的SmCtSOD模型，但最有趣的SmCtSOD和人类同源物之间的结构差异驻留在用于静电指导的底物的酶活性位点的环。
Cu,Zn superoxide dismutase (Cu,Zn SOD) is an essential enzyme for protecting cells from the toxic effects of reactive oxygen species. In humans, two distinct Cu,Zn SOD genes are located on chromosomes 4 and 21 and mutations in the latter have been associated with familial amyotrophic lateral sclerosis. Similarly, schistosomes (trematode parasites responsible for the chronically debilitating disease schistosomiasis) also produce two distinct Cu,Zn SODs, in this case one cytosolic and one bearing a signal peptide. The crystal structure of the cytosolic form of the enzyme from the human trematode Schistosoma mansoni (SmCtSOD) was solved and refined to a resolution of 2.2 Angstrom (space group P2(1)2(1)2(1),R = 17.6% and R-free = 24.1%) and 1.55 Angstrom (space group P2(1), R = 15.7% and R-free = 17.1%). This is the first report of a crystal structure of a Cu,Zn superoxide dismutase derived from a human parasite. Alternate positions for the catalytic copper and its water ligand were refined for the 1.55 Angstrom SmCtSOD model, but the most interesting structural differences between SmCtSOD and the human homologue reside in the loops used for electrostatic guidance of the substrate to the enzyme active site.