Structural basis for the inhibition of firefly luciferase by a general anesthetic
Structural basis for the inhibition of firefly luciferase by a general anesthetic
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DOI：
10.1016/s0006-3495(98)77664-7
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发表时间：
1998-11-01
影响因子：
3.4
通讯作者：
Brick, P
中科院分区：
文献类型：
--
作者：
Franks, NP;Jenkins, A;Brick, P
来自pyralis Photinus的萤火虫荧光素酶可能是研究麻醉蛋白相互作用的最好的模型系统。它能在很大的效价范围内结合多种全麻药，对麻醉药表现出与动物非常相似的敏感性，并且具有可由其底物之一（ATP）调节的麻醉敏感性。在本文中，我们描述了溴仿作为全麻（在临时蛙蝌蚪）和萤火虫荧光素酶抑制剂在高和低ATP浓度的性质。此外，我们在2.2埃分辨率下描述了溴仿存在下低atp形式的荧光素酶的晶体结构。这些结果为了解该酶的麻醉抑制作用提供了结构基础，并解释了ATP对其麻醉敏感性的调节。
The firefly luciferase enzyme from Photinus pyralis is probably the best-characterized model system for studying anesthetic-protein interactions. It binds a diverse range of general anesthetics over a large potency range, displays a sensitivity to anesthetics that is very similar to that found in animals, and has an anesthetic sensitivity that can be modulated by one of its substrates (ATP). In this paper we describe the properties of bromoform acting as a general anesthetic (in Rana temporaria tadpoles) and as an inhibitor of the firefly luciferase enzyme at high and low ATP concentrations. In addition, we describe the crystal structure of the low-ATP form of the luciferase enzyme in the presence of bromoform at 2.2-Angstrom resolution. These results provide a structural basis for understanding the anesthetic inhibition of the enzyme, as well as an explanation for the ATP modulation of its anesthetic sensitivity.