Structure and activity of the only human RNase T2.
Structure and activity of the only human RNase T2.
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DOI：
10.1093/nar/gks614
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发表时间：
2012-09-01
影响因子：
14.9
通讯作者：
Krätzner R
中科院分区：
文献类型：
--
作者：
Thorn A;Steinfeld R;Ziegenbein M;Grapp M;Hsiao HH;Urlaub H;Sheldrick GM;Gärtner J;Krätzner R
人类核糖核酸酶T2基因突变与人类大脑的白色物质疾病有关。虽然大脑异常（双侧颞叶囊肿和多灶性白色病变）和临床症状（精神障碍，痉挛和癫痫）的特点，RNase T2缺乏症的病理机制仍不清楚。RNase T2是Rh/T2/S酸性水解酶家族的唯一成员。近年来，已经报道了与其催化活性无关的新功能，例如RNase T2的肿瘤抑制特性。我们在1.6 nm分辨率下测定了人RNase T2的X射线结构。α+β核心折叠与已知的植物T2 RNA酶结构高度相似，而相比之下，外环区域显示出明显的结构差异。分析了二价阳离子存在下RNase T2的催化特征，并研究了已知临床突变的结构后果。我们的数据提供了进一步了解人类RNase T2的功能，并可能有助于了解其独立于其酶活性的作用模式。
Mutations in the gene of human RNase T2 are associated with white matter disease of the human brain. Although brain abnormalities (bilateral temporal lobe cysts and multifocal white matter lesions) and clinical symptoms (psychomotor impairments, spasticity and epilepsy) are well characterized, the pathomechanism of RNase T2 deficiency remains unclear. RNase T2 is the only member of the Rh/T2/S family of acidic hydrolases in humans. In recent years, new functions such as tumor suppressing properties of RNase T2 have been reported that are independent of its catalytic activity. We determined the X-ray structure of human RNase T2 at 1.6 Å resolution. The α+β core fold shows high similarity to those of known T2 RNase structures from plants, while, in contrast, the external loop regions show distinct structural differences. The catalytic features of RNase T2 in presence of bivalent cations were analyzed and the structural consequences of known clinical mutations were investigated. Our data provide further insight into the function of human RNase T2 and may prove useful in understanding its mode of action independent of its enzymatic activity.
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影响因子：
4.3
作者：
Mura, Cameron;McCrimmon, Colin M.;Sawaya, Michael R.
通讯作者：
Sawaya, Michael R.
影响因子：
2.9
作者：
Kawano, S;Kakuta, Y;Kimura, M
通讯作者：
Kimura, M
影响因子：
7.3
作者：
de Leeuw, Marina;Gonzalez, Ana;Almog, Orna
通讯作者：
Almog, Orna
影响因子：
7.4
作者：
NURNBERGER, T;ABEL, S;GLUND, K
通讯作者：
GLUND, K
DOI：
10.1073/pnas.1009811107
发表时间：
2011-01-18
影响因子：
11.1
作者：
Haud, Noemie;Kara, Firat;Hurlstone, Adam F. L.
通讯作者：
Hurlstone, Adam F. L.