Luong C, Miller A, Barnett J, Chow J, Ramesha C, Browner M F
Inflammatory Diseases Unit, Roche Bioscience, Palo Alto, California 94303, USA.
Nat Struct Biol. 1996 Nov;3(11):927-33. doi: 10.1038/nsb1196-927.
The first crystal structure of human cyclooxygenase-2, in the presence of a selective inhibitor, is similar to that of cyclooxygenase-1. 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.
在存在选择性抑制剂的情况下，人环氧化酶-2的首个晶体结构与环氧化酶-1的晶体结构相似。非甾体抗炎药（NSAID）结合位点的结构也高度保守，尽管其整体大小和形状存在差异，这些差异可用于选择性COX-2抑制剂的进一步开发。具有不同结合抑制剂的第二个COX-2结构在NSAID结合位点底部呈现出一种新的开放构象，而COX-2结构的其他区域没有明显变化。这两个COX-2结构为环氧化酶的柔性本质提供了证据，揭示了底物和抑制剂如何从膜内进入环氧化酶活性位点的细节。
