Crystal structure of human wildtype and S581L-mutant glycyl-tRNA synthetase, an enzyme underlying distal spinal muscular atrophy
Crystal structure of human wildtype and S581L-mutant glycyl-tRNA synthetase, an enzyme underlying distal spinal muscular atrophy
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DOI：
10.1016/j.febslet.2007.05.046
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发表时间：
2007-06-26
期刊：
影响因子：
3.5
通讯作者：
Stammers, David K.
中科院分区：
文献类型：
--
作者：
Cader, Muhammed Z.;Ren, Jingshan;Stammers, David K.
普遍存在的酶甘氨酰-tRNA合成酶（GlyRS）（包括S581 L）的显性突变导致运动神经变性。我们已经确定了野生型和S581 L突变的人GlyRS的晶体结构。S581 L突变与活性位点的50 A相似，但氨酰化活性降低。野生型和S581 L-GlyRS的整体结构，包括活性位点，非常相似。然而，反密码子结合结构域的残基567-575移动位置，进而可以通过tRNA间接影响甘氨酸结合或抑制构象变化。酶活性降低可能是神经元变性的基础，尽管在这种常染色体显性遗传病中更可能是显性-负效应。(c)2007年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Dominant mutations in the ubiquitous enzyme glycyl-tRNA synthetase (GlyRS), including S581L, lead to motor nerve degeneration. We have determined crystal structures of wildtype and S581L-mutant human GlyRS. The S581L mutation is similar to 50 A from the active site, and yet gives reduced aminoacylation activity. The overall structures of wildtype and S581L-GlyRS, including the active site, are very similar. However, residues 567-575 of the anticodon-binding domain shift position and in turn could indirectly affect glycine binding via the tRNA or alternatively inhibit conformational changes. Reduced enzyme activity may underlie neuronal degeneration, although a dominant-negative effect is more likely in this autosomal dominant disorder. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.