Prediction of reduction potential changes in rubredoxin: a molecular mechanics approach.
Prediction of reduction potential changes in rubredoxin: a molecular mechanics approach.
复制标题
红氧还蛋白还原电位变化的预测：分子力学方法。
DOI：
10.1016/s0006-3495(03)74705-5
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Ichiye,Toshiko
中科院分区：
文献类型：
--
作者：
Ergenekan,CanE;Thomas,Dustin;Fischer,JustinT;Tan,Ming-Liang;Eidsness,MarlyK;Kang,ChulHee;Ichiye,Toshiko
预测突变对蛋白质还原电位的影响对于理解蛋白质环境如何调节还原电位至关重要。此前，我们提出，残基 44 处的丙氨酸与缬氨酸会导致同源红氧还蛋白中的还原电位存在 50 mV 的差异，因为由于侧链大小不同，极性主链相对于铁位点发生了移动。此处，目的是确定残基 44 处的甘氨酸、异亮氨酸和亮氨酸突变对红氧还蛋白的结构和还原潜力的影响，以及这些影响是否与侧链大小成正比。野生型和突变型巴氏梭菌红氧还蛋白的晶体结构分析、分子力学模拟和实验还原电位，以及同源红氧还蛋白的序列分析表明，相对于氧化还原位点的主链位置以及氧化还原位点附近的溶剂渗透都是还原电位的结构决定因素，尽管与侧链大小不成比例。因此，蛋白质相互作用太复杂，无法通过简单的关系来预测，这表明分子力学方法在理解它们方面的实用性。
Predicting the effects of mutation on the reduction potential of proteins is crucial in understanding how reduction potentials are modulated by the protein environment. Previously, we proposed that an alanine vs. a valine at residue 44 leads to a 50-mV difference in reduction potential found in homologous rubredoxins because of a shift in the polar backbone relative to the iron site due to the different side-chain sizes. Here, the aim is to determine the effects of mutations to glycine, isoleucine, and leucine at residue 44 on the structure and reduction potential of rubredoxin, and if the effects are proportional to side-chain size. Crystal structure analysis, molecular mechanics simulations, and experimental reduction potentials of wild-type and mutantClostridium pasteurianumrubredoxin, along with sequence analysis of homologous rubredoxins, indicate that the backbone position relative to the redox site as well as solvent penetration near the redox site are both structural determinants of the reduction potential, although not proportionally to side-chain size. Thus, protein interactions are too complex to be predicted by simple relationships, indicating the utility of molecular mechanics methods in understanding them.