Department of Physics and Center for Mathematical Biosciences, Indiana University-Purdue University at Indianapolis, Indianapolis, IN, USA.
Phys Biol. 2009 Dec 11;7:16002. doi: 10.1088/1478-3975/7/1/016002.
The source of increased stability in proteins from organisms that thrive in extreme thermal environments is not well understood. Previous experimental and theoretical studies have suggested many different features possibly responsible for such thermostability. Many of these thermostabilizing mechanisms can be accounted for in terms of structural rigidity. Thus a plausible hypothesis accounting for this remarkable stability in thermophilic enzymes states that these enzymes have enhanced conformational rigidity at temperatures below their native, functioning temperature. Experimental evidence exists to both support and contradict this supposition. We computationally investigate the relationship between thermostability and rigidity using rubredoxin as a case study. The mechanical rigidity is calculated using atomic models of homologous rubredoxin structures from the hyperthermophile Pyrococcus furiosus and mesophile Clostridium pasteurianum using the FIRST software. A global increase in structural rigidity (equivalently a decrease in flexibility) corresponds to an increase in thermostability. Locally, rigidity differences (between mesophilic and thermophilic structures) agree with differences in protection factors.
在极端热环境中生存的生物体的蛋白质稳定性增加的原因尚不清楚。先前的实验和理论研究表明，许多不同的特征可能与其热稳定性有关。许多这些热稳定机制可以用结构刚性来解释。因此，一个可以解释嗜热酶这种显著稳定性的合理假设是，这些酶在低于其天然功能温度时具有增强的构象刚性。实验证据既支持也反驳了这一假设。我们使用 rubredoxin 作为案例研究，计算研究了热稳定性和刚性之间的关系。使用 FIRST 软件，根据来自高温古菌 Pyrococcus furiosus 和中温菌 Clostridium pasteurianum 的同源 rubredoxin 结构的原子模型，计算出机械刚性。结构刚性的整体增加（相当于柔韧性的降低）对应于热稳定性的增加。局部刚性差异（在中温和嗜热结构之间）与保护因子的差异一致。
