一种全身麻醉剂抑制萤火虫荧光素酶的结构基础。
Structural basis for the inhibition of firefly luciferase by a general anesthetic.
作者信息
Franks N P, Jenkins A, Conti E, Lieb W R, Brick P
机构信息
Biophysics Section, The Blackett Laboratory, Imperial College of Science, Technology and Medicine, London, England.
出版信息
Biophys J. 1998 Nov;75(5):2205-11. doi: 10.1016/S0006-3495(98)77664-7.
Abstract
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-A 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.
摘要
来自北美萤火虫的萤火虫荧光素酶可能是研究麻醉剂与蛋白质相互作用的特征最明显的模型系统。它能在很大的效能范围内结合多种全身麻醉剂，对麻醉剂的敏感性与在动物体内发现的非常相似，并且其麻醉敏感性可被其一种底物（ATP）调节。在本文中，我们描述了溴仿在高ATP浓度和低ATP浓度下作为全身麻醉剂（在林蛙蝌蚪中）以及作为萤火虫荧光素酶抑制剂的特性。此外，我们还描述了在存在溴仿的情况下，荧光素酶低ATP形式的晶体结构，分辨率为2.2埃。这些结果为理解该酶的麻醉抑制作用提供了结构基础，也为其麻醉敏感性的ATP调节提供了解释。
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