大肠杆菌硝基还原酶的结构与烟酸:三个水晶形式为1.7、1.8和2.4的决议。
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情人,海德EI塞尔PF,白色SA
大肠杆菌硝基还原酶的结构与烟酸:三个水晶形式为1.7、1.8和2.4的决议。
J杂志。2001年5月25日,309(1):203 - 13所示。
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11491290 (在PubMed]
- 文摘
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大肠杆菌硝基还原酶是一种黄素蛋白,减少各种醌和硝基芳香化合物基质。其转换能力相对无毒的高活性化合物如CB1954 (5 - [aziridin-1-yl] 2, 4-dinitrobenzamide)到高细胞毒性衍生品导致癌症基因治疗其潜在的兴趣。我们已经确定酶的结构绑定到一个底物类似物,烟酸,从三个水晶形式1.7决议,1.8和2.4,代表十non-crystallographically相关单体。酶是二聚的,有一个大的疏水核心;每个分子由一个five-strandedβ褶板的一半被阿尔法螺旋包围。螺旋F和F突出每个单体的核心区域。有一个广泛的二聚体界面,15 c端残留在反对延长单体,第五beta-strand作出贡献。活动地点位于分子的两端,在石穴solvent-exposed二聚体界面。FMN一个单体之间形成氢键和疏水接触两种;如果脸埋。 The nicotinic acid stacks between the re face of the FMN and Phe124 in helix F, with only one hydrogen bond to the protein. If the nicotinamide ring of the coenzyme NAD(P)H were in the same position as that of the nicotinic acid ligand, its C4 atom would be optimally positioned for direct hydride transfer to flavin N5. Comparison of the structure with unliganded flavin reductase and NTR suggests reduced mobility of helices E and F upon ligand binding. Analysis of the structure explains the broad substrate specificity of the enzyme, and provides the basis for rational design of novel prodrugs and for site-directed mutagenesis for improved enzyme activity.