甲氧苄啶与二氢叶酸还原酶结合的动力学
Dynamics of trimethoprim bound to dihydrofolate reductase.
作者信息
Searle M S, Forster M J, Birdsall B, Roberts G C, Feeney J, Cheung H T, Kompis I, Geddes A J
机构信息
Division of Physical Biochemistry, National Institute for Medical Research, London, United Kingdom.
出版信息
Proc Natl Acad Sci U S A. 1988 Jun;85(11):3787-91. doi: 10.1073/pnas.85.11.3787.
Abstract
The conformation of a small molecule in its binding site on a protein is a major factor in the specificity of the interaction between them. In this paper, we report the use of 1H and 13C NMR spectroscopy to study the fluctuations in conformation of the anti-bacterial drug trimethoprim when it is bound to its "target," dihydrofolate reductase. 13C relaxation measurements reveal dihedral angle changes of +/- 25 degrees to +/- 35 degrees on the subnanosecond time scale, while 13C line-shape analysis demonstrates dihedral angle changes of at least +/- 65 degrees on the millisecond time scale. 1H NMR shows that a specific hydrogen bond between the inhibitor and enzyme, which is believed to make an important contribution to binding, makes and breaks rapidly at room temperature.
摘要
小分子在蛋白质结合位点的构象是它们之间相互作用特异性的主要因素。在本文中，我们报道了利用¹H和¹³C核磁共振光谱来研究抗菌药物甲氧苄啶与它的“靶标”二氢叶酸还原酶结合时构象的波动情况。¹³C弛豫测量揭示了在亚纳秒时间尺度上二面角有±25度到±35度的变化，而¹³C线形分析表明在毫秒时间尺度上二面角至少有±65度的变化。¹H核磁共振显示抑制剂与酶之间的一个特定氢键在室温下迅速形成和断裂，据信该氢键对结合有重要贡献。
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