External and internal electrostatic potentials of cholinesterase models
External and internal electrostatic potentials of cholinesterase models
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DOI：
10.1016/s1093-3263(98)00005-9
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发表时间：
1997-10-01
影响因子：
2.9
通讯作者：
Sussman, JL
中科院分区：
文献类型：
--
作者：
Felder, CE;Botti, SA;Sussman, JL
在泊松-玻尔兹曼方程的基础上，采用Delphi算法计算了不同种类胆碱酯酶三维结构的静电电位。我们利用加利福尼亚鱼雷和小鼠乙酰胆碱酯酶的结构，建立了人类、Bungarus fasciatus和Drosophila melanogaster乙酰胆碱酯酶和人类丁酰胆碱酯酶的同源模型。所有这些结构都显示出负的外表面电位，在活动场地峡谷入口附近的区域，随着峡谷边缘的接近，这种电位变得更加负。此外，在所有情况下，沿着峡谷中轴线向下的电位变得越来越负，在靠近活动场地的峡谷底部最大。来自不同物种的AChE序列比对中保守的10个关键酸性残基，无论是在活性位点峡谷入口附近的表面区域还是在其底部，似乎都是这些电位的主要原因。所检查的结构之间的电位高度相关，序列同一性低至35%。这表明它们是胆碱酯酶家族的一个保守特性，可以吸引带正电荷的底物进入和进入活性位点，并且可能对胆碱酯酶的功能起重要作用。(C) 1998年Elsevier Science Inc。
The electrostatic potentials for the three-dimensional structures of cholinesterinases from various species were calculated, using the Delphi algorithm, on the basis of the Poisson-Boltzmann equation. We used structures for Torpedo californica and mouse acetylcholinesterase, and built homology models of the human, Bungarus fasciatus, and Drosophila melanogaster acetylcholinesterases and human butyrylcholinesterase. All these structures reveal a negative external surface potential, in the area around the entrance to the active-site gorge, that becomes more negative as the rim of the gorge is approached. Moreover in all cases, the potential becomes increasingly more negative along the central axis running down the gorge, and is largest at the base of` the gorge, near the active site. Ten key acidic residues conserved in the sequence alignments of AChE from various species, both in the surface area near the entrance of the active-site gorge and at its base, appear to be primarily responsible for these potentials. The potentials are highly correlated among the structures examined, down to sequence identities as low as 35%. This indicates that they are a conserved property of the cholinesterase family could serve to attract the positively charged substrate into and down the gorge to the active site, and may play other roles important for cholinesterase function. (C) 1998 by Elsevier Science Inc.