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| 1 | Study on structure-activity relationship of mutation-dependent herbicide resistance acetohydroxyacid synthase through 3D-QSAR and mutation显示文摘Seventy-four sulfonylureas were synthesized and tested for their inhibitory activity against the whole enzyme of E. coli acetohydroxyacid synthase (AHAS, EC 2.2.1.6) isoenzyme II, and 3D-QSAR analyses were performed based on these inhibitory activities. The binding conformation of chlorimuron-ethyl, a commercial herbicide of AHAS, in the crystal structure of AHAS complex was extracted and used as template to build the initial three-dimensional structure of other sulfonylureas, and then all structures were fully geometry optimized. After systematic optimization of the alignment rule, molecular orienta- tion, grid space and attenuation factor, two satisfactory models with excellent performances (CoMFA: q2 = 0.735, r2 = 0.954, n = 7, r 2 pred = 0.832; CoMSIA: q2 = 0.721, r2 = 0.913, n = 8, r 2pred = 0.844) were estab- lished. By mapping the 3D contour maps of CoMFA and CoMSIA models into the possible inhibitory active site in the crystal structure of catalytic subunit of yeast AHAS, a plausible binding model for AHAS, with best fit QSAR in the literature so far, was proposed. Moreover, the results of 3D-QSAR were further utilized to interpret resistance of site-directed mutants. A relative activity index (RAI) for AHAS enzyme mutant was defined for the first time to relate the 3D-QSAR and resistance of mutants. This study, for the first time, demonstrated that combination of 3D-QSAR and enzyme mutation can be used to decipher the molecular basis of ligand-receptor interaction mechanism. This study refined our understanding of the ligand-receptor interaction and resistance mechanism in AHAS-sulfonylurea system, and provided basis for designing new potent herbicides to combat the herbicide resistance. | YU ZhiHong NIU CongWei BAN ShuRong WEN Xin XI Zhen | 2007 | Chinese Science Bulletin2007，52，14： | 5 |
| 2 | Homologous and heterologous interactions between catalytic and regulatory subunits of Escherichia coli acetohydroxyacid synthaseⅠand Ⅲ显示文摘Homologous and heterologous interactions between acetohydroxyacid synthase (AHAS) I and Ⅲ from E. coli have been studied by surface plasmon resonance (SPR). The catalytic and regulatory subunits association for AHAS I (KD = 1.13 × 10-7 M) was stronger than that for AHAS Ⅲ (KD = 5.29 × 10-7 M). A strong heterologous association between regulatory and catalytic subunits and heterologous activation of catalytic subunits were observed. SPR results combined with enzyme kinetics indicate that the reconstituted heterologous enzymes had similar kinetic properties as homologous enzymes, implying that the regulatory subunit of AHAS I could be replaced by the regulatory subunit of AHAS Ⅲ and vice versa. This work may be useful to further understandings of the mechanism of regulation of AHAS. | NIU CongWei, FENG Wei, ZHOU YanFei, WEN Xin & XI Zhen State Key Laboratory of Elemento-Organic Chemistry and Department of Chemical Biology, Nankai University, Tianjin 300071, China | 2009 | Science China Chemistry2009，52，9： | 3 |
| 3 | Development of a general quantum-chemical descriptor for steric effects: density functional theory based QSAR study of herbicidal sulfonylurea analogues显示文摘 | XI Zhen YU Zhihong NIU Congwei | 2006 | J Comput Chem2006，27，13： | 1 |
| 4 | Computational design and discovery of conformationally flexible inhibitors of acetohydroxyacid synthase to overcome drug resistance associated with the W586L mutation 显示文摘 | JI Fengqin NIU Congwei CHEN Chaonan | 2008 | Chem Med Chem2008，3，8： | 1 |
| 5 | Molecular Drug Resistance Prediction for Acetohydroxyacid Synthase Mutants Against Chlorsulfuron Using MB-QSAR显示文摘Chlorsulfuron 是首先商品化的 sulfonylurea 除草剂,它指向 acetohydroxyacid synthase (啊哈) 。在啊哈的变化引起了严肃的除草剂抵抗到 chlorsulfuron。对在分子的水平的除草剂抵抗的量的描述将有益于抵抗机制的理解并且帮助躲避抵抗的除草剂的设计。我们最近建立了 MB-QSAR (变化依赖者 Biomacromolecular 量的结构活动关系) 在 biomacromolecules 进行 3D-QSAR 学习的方法。基于对 chlorsulfuron 为一系列啊哈异种测量的除草剂抵抗数据,此处,我们构造了 MB-QSAR 模型到份量上预言除草剂抵抗并且对 chlorsulfuron 为啊哈异种解释结构抵抗关系。相当好关联在之间试验性并且预言的 pKi 价值为 MB-QSAR/CoMFA 被完成(q2=0.705, r2=0.918, r2pred=0.635 ) 并且 MB-QSAR/CoMSIA (q2=0.558, r2=0.940, r2pred=0.527 ) MB-QSAR 模型的模型,和解释给了化学直觉的信息指导躲避抵抗的除草剂设计。 | Yinwu He Congwei Niu Xin Wen Zhen Xi | 2013 | Chinese Journal of Chemistry2013，31，9： | 1 |
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