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首页> 外文期刊>Biochemistry >Effects of histidine protonation and phosphorylation on histidine-containing phosphocarrier protein structure, dynamics, and physicochernical properties
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Effects of histidine protonation and phosphorylation on histidine-containing phosphocarrier protein structure, dynamics, and physicochernical properties

机译：组氨酸质子化和磷酸化对含组氨酸的磷酸载体蛋白结构，动力学和物理化学性质的影响

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Previous structural studies of the histidine-containing phosphocarrier protein (HPr) have shown that active site residue His 15 can adopt two distinct conformations which were termed OPEN and CLOSED. Using molecular dynamics simulations and protonation probability calculations, we were able to show that these two conformations correspond to different protonation forms of the histidine ring. The CLOSED-to-OPEN transition requires His 15 to adopt a conformation with higher energy, which is compensated by the favorable energetic consequences of protonation. Calculations of the conformational energy of His15 show that HPr exists mainly in the CLOSED form at pH 7. The very low apparent pK(a) value (3.2-4.5) of the CLOSED conformation and the fact that the imidazole ring of residue 15 is primarily unprotonated at N delta 1 at neutral pH ensure that His15 is ideally primed to be specifically phosphorylated at N delta 1. In contrast to unphosphorylated HPr, the phosphorylated form exhibits, no conformational transitions, and the CLOSED state is stable even for the protonated imidazole ring due to favorable interactions between the phosphate group and the backbone of Ala 16 and Arg 17. These observations from MD simulations are confirmed by a simple four-microstate model which can explain both the pH-dependent conformational change of unphosphorylated HPr and the conformational rigidity of phosphorylated HPr. Our study suggests that the predominant CLOSED conformation is relevant for HPr function in the phosphotransfer reaction, while the OPEN form of unphosphorylated HPr might be important for its additional regulatory function, in which an OPEN conformation of His15 is recognized by the transcriptional regulator CcpA.
机译：以前对含组氨酸的磷酸载体蛋白（HPr）的结构研究表明，活性位点残基His 15可以采用两个不同的构象，分别称为OPEN和CLOSED。使用分子动力学模拟和质子化概率计算，我们能够证明这两个构象对应于组氨酸环的不同质子化形式。从闭合到打开的过渡要求His 15采取更高能量的构象，而质子化的有利能量后果对此进行了补偿。 His15的构象能的计算表明，HPr主要在pH 7下以闭合形式存在。闭合构象的非常低的表观pK（a）值（3.2-4.5）和残基15的咪唑环主要是在中性pH下在Nδ1处未质子化可确保His15在Nδ1处进行理想的底物磷酸化。与未磷酸化的HPr相比，磷酸化形式无构象转变，即使对于质子化的咪唑环，闭合态也稳定由于磷酸基团与Ala 16和Arg 17的骨架之间存在有利的相互作用，因此通过简单的四微状态模型证实了这些来自MD模拟的观察结果，该模型可以解释未磷酸化HPr的pH依赖性构象变化和Pr的构象刚性。磷酸化的HPr。我们的研究表明，主要的CLOSED构象与磷酸转移反应中的HPr功能有关，而未磷酸化的HPr的OPEN形式可能对其额外的调节功能很重要，其中His15的OPEN构象被转录调节子CcpA识别。

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