...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Acta crystallographica.Section D. Biological crystallography >Structures of human constitutive nitric oxide synthases
【24h】

Structures of human constitutive nitric oxide synthases

机译：人类本构一氧化氮的结构synthases

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Mammals produce three isoforms of nitric oxide synthase (NOS): neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). The overproduction of NO by nNOS is associated with a number of neurodegenerative disorders; therefore, a desirable therapeutic goal is the design of drugs that target nNOS but not the other isoforms. Crystallography, coupled with computational approaches and medicinal chemistry, has played a critical role in developing highly selective nNOS inhibitors that exhibit exceptional neuroprotective properties. For historic reasons, crystallography has focused on rat nNOS and bovine eNOS because these were available in high quality; thus, their structures have been used in structure-activity-relationship studies. Although these constitutive NOSs share more than 90% sequence identity across mammalian species for each NOS isoform, inhibitor-binding studies revealed that subtle differences near the heme active site in the same NOS isoform across species still impact enzyme-inhibitor interactions. Therefore, structures of the human constitutive NOSs are indispensible. Here, the first structure of human neuronal NOS at 2.03 angstrom resolution is reported and a different crystal form of human endothelial NOS is reported at 1.73 angstrom resolution.
机译：哺乳动物产生一氧化氮的三个亚型合酶(NOS):神经元NOS (nNOS),诱导(我们)和endothelial我们(eNOS)。生产过剩的没有nNOS与相关联许多神经退行性疾病;一个理想的治疗目标是设计药物目标nNOS而不是其他亚型。计算方法和药物化学,发挥了至关重要的作用在发展中高度选择性nNOS抑制剂,展览特殊神经保护属性。历史原因,晶体学关注老鼠nNOS和牛以挪士,因为这些都是提供高质量;已经被使用在构效关系研究。超过90%的序列在哺乳动物的身份inhibitor-binding物种为每个号同种型研究表明,在微妙的差异血红素活性部位在同一号同种型物种仍影响酶抑制剂交互。本构诺是不可或缺的。人类神经元NOS在2.03的第一个结构埃分辨率和不同的报道晶体形式的人类内皮号报道为1.73埃分辨率。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号