蛋白质中的金属结合点中的第一秒外相互作用:PDB调查和DFT/CDM计算
Todor Dudev1, Yen-lin Lin, Minko Dudev
1Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan ROC.
研究表明,金属蛋白的第二层外,主要是酸骨干和特定的氨基酸侧链,显著影响金属离子的结合和选择性. 这一外层稳定了内部的协调外,并补充了它的特性.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 计算化学的计算化学
背景情况:
- 金属蛋白利用特定的金属离子进行各种生物功能.
- 协调环境,包括第二层外,对于金属结合和选择性至关重要.
- 了解这些相互作用有助于设计金属酶模仿剂和治疗方法.
研究的目的:
- 阐明第二个外在金属结合和金属蛋白选择性中的作用.
- 为了识别常见的Mg,Mn,Ca和Zn的第二层联体.
- 为了研究第二层外对金属离子歧视的贡献.
主要方法:
- 蛋白质数据库 (PDB) 对Mg,Mn,Ca和Zn结合点的调查.
- 密度函数理论/连续介电方法 (DFT/CDM) 的计算.
- 对键和静电相互作用的分析.
主要成果:
- 骨干组是最常见的第二层联体,其次是Asp/Glu,Lys/Arg,Asn/Gln和Ser/Thr.
- 芳香和含硫的侧链很少在第二个外中发现.
- 第二个外,特别是Asp/Glu,影响金属联体质子和稳定金属复合体.
- 第二层相互作用通过基于离子半径和几何学的区分,有助于金属的选择性.
- 第一个和第二个外之间的相互作用能量随着溶剂暴露而衰变,但与第一个外的相互作用相当.
结论:
- 第二个外的结构和特性是由第一个协调外决定的.
- 第二个外稳定和保护内部外,增强其功能.
- 第二的组成对金属离子选择性和金属蛋白的结合亲和性至关重要.
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