天冬氨酸氨甲酰基转移酶的分子动力学模拟与刚体（TLS）分析：非偶联R态的证据
Molecular dynamics simulations and rigid body (TLS) analysis of aspartate carbamoyltransferase: evidence for an uncoupled R state.
作者信息
Tanner J J, Smith P E, Krause K L
机构信息
Department of Biochemistry and Biophysical Sciences, University of Houston, Texas 77204-5934.
出版信息
Protein Sci. 1993 Jun;2(6):927-35. doi: 10.1002/pro.5560020606.
Abstract
In the R form of ATCase complexed with the bisubstrate analogue, N-(phosphonacetyl)-L-aspartate, large temperature factors are reported for the allosteric domains of the regulatory chains. We studied the conformational flexibility of the holoenzyme with molecular dynamics simulations and rigid body (TLS) analysis. The results of the molecular dynamics simulations suggest that, although local atomic fluctuations account for the temperature factors of the catalytic and zinc domains, they do not account for the large temperature factors of the allosteric regions. However, the temperature factors of the allosteric domains can be satisfactorily analyzed using a rigid body model. The simulations and rigid body analysis support the idea that the allosteric regions are mechanically uncoupled from the rest of the enzyme in the PALA structure. Implications of this uncoupling for allosteric regulation are discussed.
摘要
在与双底物类似物N-（膦酰乙酰基）-L-天冬氨酸复合的天冬氨酸转氨甲酰酶（ATCase）的R形式中，据报道调节链的变构结构域具有较大的温度因子。我们用分子动力学模拟和刚体（TLS）分析研究了全酶的构象灵活性。分子动力学模拟结果表明，虽然局部原子涨落解释了催化结构域和锌结构域的温度因子，但它们并不能解释变构区域较大的温度因子。然而，变构结构域的温度因子可以用刚体模型得到满意的分析。模拟和刚体分析支持了在PALA结构中变构区域与酶的其余部分在机械上解偶联的观点。讨论了这种解偶联对变构调节的影响。
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