Finding gas diffusion pathways in proteins:: Application to O2 and H2 transport in Cpl [FeFe]-hydrogenase and the role of packing defects
Finding gas diffusion pathways in proteins:: Application to O2 and H2 transport in Cpl [FeFe]-hydrogenase and the role of packing defects
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DOI：
10.1016/j.str.2005.05.013
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发表时间：
2005-09-01
期刊：
影响因子：
5.7
通讯作者：
Schulten, K
中科院分区：
文献类型：
--
作者：
Cohen, J;Kim, K;Schulten, K
我们报告了外部溶液与巴氏梭菌 Cpl [FeFe]-氢化酶产氢活性位点之间 H-2 和 O-2 被动运输的计算研究。讨论并应用了两种不同的研究气体进入的方法：（1）温度控制的局部增强采样，（2）体积溶剂可进入图，提供一致的结果。两种方法都证实了先前假设的途径的存在和功能，并揭示了先前对 Cpl 静态晶体结构的分析未检测到的第二个主要途径。我们的结果表明，在 Cpl 内部扩散的疏水性小分子（例如 H-2 和 O-2）利用了明确的预先存在的堆积缺陷，这些缺陷从蛋白质的静态结构中并不总是显而易见，但可以从蛋白质的动态运动中预测。最后，我们描述了 H-2 和 O-2 的两种截然不同的蛋白质内运输模式，在我们的模型中，它们仅通过大小来区分。
We report on a computational investigation of the passive transport of H-2 and O-2 between the external solution and the hydrogen-producing active site of Cpl [FeFe]-hydrogenase from Clostridium pasteurianum. Two distinct methodologies for studying gas access are discussed and applied: (1) temperature-controlled locally enhanced sampling, and (2) volumetric solvent accessibility maps, providing consistent results. Both methodologies confirm the existence and function of a previously hypothesized pathway and reveal a second major pathway that had not been detected by previous analyses of Cpl's static cry tal structure. Our results suggest that small hydrophobic molecules, such as H-2 and O-2, diffusing inside Cpl, take advantage of well-defined preexisting packing defects that are not always apparent from the protein's static structure, but that can be predicted from the protein's dynamical motion. Finally, we describe two contrasting modes of intraprotein transport for H-2 and O-2, which in our model are differentiated only by their size.