Flexibility of the NSAID binding site in the structure of human cyclooxygenase-2
Flexibility of the NSAID binding site in the structure of human cyclooxygenase-2
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DOI：
10.1038/nsb1196-927
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发表时间：
1996-11-01
期刊：
影响因子：
--
通讯作者：
Browner, MF
中科院分区：
文献类型：
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作者：
Luong, C;Miller, A;Browner, MF
在选择性抑制剂的作用下，人环加氧酶-2的第一个晶体结构与环加氧酶- 1相似。NSAID结合位点的结构也很保守，尽管其总体大小和形状存在差异，这可能用于进一步开发选择性COX-2抑制剂。具有不同结合抑制剂的第二种COX-2结构在NSAID结合位点的底部显示出新的开放构象，COX-2结构的其他区域没有明显变化。这两种COX-2结构为环加氧酶的柔韧性提供了证据，揭示了底物和抑制剂如何从膜内进入环加氧酶活性位点的细节。
The first crystal structure of human cyclooxygenase-2, in the presence of a selective inhibitor, is similar to that of cyclooxygenase-l. The structure of the NSAID binding site is also well conserved, although there are differences in its overall size and shape which may be exploited for the further development of selective COX-2 inhibitors. A second COX-2 structure with a different bound inhibitor displays a new, open conformation at the bottom of the NSAID binding site, without significant changes in other regions of the COX-2 structure. These two COX-2 structures provide evidence for the flexible nature of cyclooxygenase, revealing details about how substrate and inhibitor may gain access to the cyclooxygenase active site from within the membrane.