Determination of protein-ligand binding modes using complexation-induced changes in 1H NMR chemical shift
Determination of protein-ligand binding modes using complexation-induced changes in 1H NMR chemical shift
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DOI：
10.1021/jm701194r
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发表时间：
2008-04-24
影响因子：
7.3
通讯作者：
Spitaleri, Andrea
中科院分区：
文献类型：
--
作者：
Cioffi, Marina;Hunter, Christopher A.;Spitaleri, Andrea
介绍了一种利用H-1核磁共振化学位移（CIS）实验测定络合诱导变化来测定蛋白质-配体配合物三维溶液结构的新方法。该方法已通过抗肿瘤抗生素neocarzinostatin （NCS）蛋白与合成的发色团类似物之间形成的复合物进行了验证。未结合蛋白的x射线晶体结构和主酰胺质子CIS是确定配合物三维结构的输入数据。将实验CIS值用于基于遗传算法的连续直接结构优化过程中，对构象空间进行采样。计算得到的配合物结构与核磁共振溶液结构吻合较好，表明了该方法在结构测定方面的潜力。
A new method for determining three-dimensional solution structures of protein-ligand complexes using experimentally determined complexation-induced changes in H-1 NMR chemical shift (CIS) is introduced. The method has been validated using the complex formed between the protein antitumor antibiotic neocarzinostatin (NCS) and a synthetic chromophore analogue. The X-ray crystal structure of the unbound protein and the backbone amide proton CIS were the input data used in the determination of the three-dimensional structure of the complex. The experimental CIS values were used in a continuous direct structure refinement process based on genetic algorithms to sample conformational space. The calculated structure of the complex agrees well with the NMR solution structure, indicating the potential of this approach for structure determination.