NMR structural characterization of the penta-peptide calpain inhibitor.
NMR structural characterization of the penta-peptide calpain inhibitor.
复制标题
五肽钙蛋白酶抑制剂的 NMR 结构表征。
DOI：
10.1016/j.febslet.2008.11.037
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发表时间：
2009
期刊：
影响因子：
3.5
通讯作者：
Vinogradova,Olga
中科院分区：
文献类型：
--
作者：
Deshmukh,Lalit;Wu,Liping;Guttmann,RodneyP;Vinogradova,Olga
钙蛋白酶是细胞内普遍存在的钙和巯基依赖性蛋白酶。它们的过度活化，导致各种底物的降解，与许多心血管和神经系统疾病有关。在这里，我们提出了LSEAL五肽的第一个结构表征，LSEAL五肽是一种有效的钙蛋白酶抑制剂，与钙蛋白酶的钙调蛋白样结构域结合。我们的体外结合数据支持这样的想法，即除了钙蛋白酶活性位点之外的结构域可能是未来开发用于治疗心脏病发作、创伤性脑损伤或各种神经退行性疾病（如缺血性中风）的治疗剂的合适靶点。
Calpains are ubiquitous intracellular calcium- and thiol-dependent proteases. Their over activation, resulting in the degradation of various substrates, has been implicated in a number of cardiovascular and neurological disorders. Here, we present the first structural characterization of LSEAL penta-peptide, a potent calpain inhibitor, bound to the calmodulin-like domain of calpain. Our in vitro binding data supports the idea that domains other than calpain’s active site may be suitable targets for future development of therapeutic agents to be used to treat heart attack, traumatic brain injuries or a variety of neurodegenerative conditions, such as ischemic stroke.