Coupling of protonation, reduction, and conformational change in azurin from Pseudomonas aeruginosa investigated with free energy measures of cooperativity.
Coupling of protonation, reduction, and conformational change in azurin from Pseudomonas aeruginosa investigated with free energy measures of cooperativity.
复制标题
使用协同自由能测量研究了铜绿假单胞菌中天青蛋白的质子化、还原和构象变化的耦合。
DOI：
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发表时间：
2011
影响因子：
3.3
通讯作者：
G. Ullmann
中科院分区：
文献类型：
--
作者：
R. Ullmann;G. Ullmann
我们在连续静电模型中使用自由能计算来分析铜绿假单胞菌（PaAz）中azurin的质子化、还原和构象变化的耦合。采用多种实验方法对PaAz进行了广泛的表征。实验确定的pK(a)值和ph依赖性还原电位用于验证我们的计算模型。从实验可知，铜中心的还原与至少两个可滴定残基（His-35和His-83）的质子化以及亲-36和Gly-37之间肽键的翻转有关。利用协同性的自由能测度详细分析了PaAz中质子化、还原和构象变化之间的耦合。铜中心的还原、His-35的质子化和肽翻转是协同的。我们的研究结果表明，协同自由能在检测和量化生物分子系统中事件之间的热力学耦合方面是有用的。发现His-35的质子化和肽翻转是如此紧密耦合，这些事件有效地协同发生。这种一致的变化导致azurin的静电表面电位的显著改变，这可能会影响azurin与其结合伙伴的相互作用。
We used free energy calculations within a continuum electrostatics model to analyze the coupling of protonation, reduction, and conformational change in azurin from Pseudomonas aeruginosa (PaAz). PaAz was characterized extensively with a variety of experimental methods. Experimentally determined pK(a) values and pH-dependent reduction potentials are used to validate our computational model. It is well-known from experiment that the reduction of the copper center is coupled to the protonation of at least two titratable residues (His-35 and His-83) and to the flip of the peptide bond between Pro-36 and Gly-37. Free energy measures of cooperativity are used for a detailed analysis of the coupling between protonation, reduction, and conformational change in PaAz. The reduction of the copper center, the protonation of His-35, and peptide flip are shown to be cooperative. Our results show that cooperativity free energies are useful in detecting and quantifying thermodynamic coupling between events in biomolecular systems. The protonation of His-35 and the peptide flip are found to be so tightly coupled that these events happen effectively concerted. This concerted change results in a marked alteration of the electrostatic surface potential of azurin that might affect the interaction of azurin with its binding partners.
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DOI：
10.1111/j.1432-1033.1993.tb18369.x
发表时间：
1993
期刊：
European journal of biochemistry
影响因子：
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作者：
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通讯作者：
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影响因子：
2.9
作者：
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通讯作者：
Davidson,VictorL
影响因子：
2.9
作者：
BASHFORD, D;CASE, DA;WRIGHT, PE
通讯作者：
WRIGHT, PE
影响因子：
2.9
作者：
Onufriev, A;Case, DA;Ullmann, GM
通讯作者：
Ullmann, GM
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影响因子：
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作者：
Ferreira,AntonioM;Bashford,Donald
通讯作者：
Bashford,Donald