Numerical simulation of aldolase tetramer stability
Numerical simulation of aldolase tetramer stability
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DOI：
10.1007/s002490050184
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发表时间：
1998-01-01
影响因子：
2
通讯作者：
Atanasov, B
中科院分区：
文献类型：
--
作者：
Miteva, M;Alexov, E;Atanasov, B
采用有限差分泊松-玻尔兹曼（FDPB）和改进的坦福德-柯克伍德（MTK）技术，利用人醛缩酶的原子坐标对醛缩酶四聚体的稳定性进行了理论研究。提出了一种计算子基间相互作用能的方法。分析了不同能量项对醛缩酶稳定性和寡聚平衡（单体双左右箭头二聚体双左右箭头四聚体）的贡献。结果表明，溶剂化能的损失和在非常高和低pH-s下的静电相互作用使低聚物不稳定。在较宽的pH范围内，由于疏水相互作用产生的稳定能补偿了这些能量项。结果表明，醛缩酶四聚体在pH值为5 ~ 11的范围内比其他低聚物更具能量优势。四聚体内亚基-亚基相互作用表明，二聚体形式是可能的子部分中最稳定的。由于这个原因，四聚体可以被认为是“二聚体的二聚体”。理论结果与实验数据的比较表明，醛缩酶四聚体在pH值3-4下的解离会导致酸变性。除了众所周知的酸性解离外，预计在高pH值（bbb12）下还会发生第二次解离。分析表明，His20或Arg257突变为中性残基可使酸性解离的pH值降低约1个pH单位。
A theoretical study of aldolase tetramer stability, conducted by finite difference Poisson-Boltzmann (FDPB) and modified Tanford-Kirkwood (MTK) techniques using the atomic coordinates of human aldolase, is described. A method for calculating the interaction energy between subunits is proposed. An analysis of the contribution of different energy terms to the stability and oligomeric equilibria (monomer double left right arrow dimer double left right arrow tetramer) of aldolase is made. It is shown that the loss of solvation energy and electrostatic interactions at very high and low pH-s destabilise the oligomers. These energy terms are compensated over a wide pH range by the stabilization energy due to hydrophobic interactions. It is shown that the aldolase tetramer is energetically more preferable than other oligomers in the pH range from 5 to 11. Subunit-subunit interactions within the tetramer suggest one dimeric form to be the most stable of the possible sub-parts. For this reason the tetramer can be thought of as a "dimer of dimers". A comparison between our theoretical results and available experimental data shows that the dissociation of the aldolase tetramer below pH 3-4 cooperatively leads to acid denaturation. A second dissociation is predicted to occur at high pH (>12) in addition to the well known acidic dissociation. The analysis suggests that a mutation of His20 or Arg257 to a neutral residue could decrease the pH of the acidic dissociation by approximately 1 pH unit.