Cioffi Marina, Hunter Christopher A, Packer Martin J, Spitaleri Andrea
Department of Chemistry, Centre for Chemical Biology, Krebs Institute for Biomolecular Science, University of Sheffield, Sheffield S3 7HF, U.K.
J Med Chem. 2008 Apr 24;51(8):2512-7. doi: 10.1021/jm701194r. Epub 2008 Mar 27.
A new method for determining three-dimensional solution structures of protein-ligand complexes using experimentally determined complexation-induced changes in (1)H 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.
介绍了一种利用实验测定的蛋白质-配体复合物的(1)H NMR化学位移络合诱导变化（CIS）来确定其三维溶液结构的新方法。该方法已通过蛋白质抗肿瘤抗生素新制癌菌素（NCS）与合成发色团类似物形成的复合物进行了验证。未结合蛋白质的X射线晶体结构和主链酰胺质子CIS是用于确定复合物三维结构的输入数据。实验CIS值用于基于遗传算法的连续直接结构优化过程，以对构象空间进行采样。复合物的计算结构与NMR溶液结构吻合良好，表明该方法在结构确定方面具有潜力。
