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Structure modeling and mutational analysis of gap junction beta 2 (GJB2)

机译:间隙连接β2(GJB2)的结构建模和突变分析

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The genome sequencing accomplishes complete genetic blue prints for hundreds of organisms, including humans. In the current era, we are trying to focus on analyzing, controlling and modifying functions of proteins encoded by these genomes. This task is attained by protein three dimensional structures. Three dimensional?(3 D)?structure is very useful for understanding biological functions. Gap junction beta 2?(GJB2),human gene encoding for gap junction beta 2?protein is involved in various hearing disorders in Pakistani families. After the first report of GJB2 involvement in Pakistani families, it was necessary to further study this protein. Therefore, a 3D structure of GJB2 was developed using comparative modeling approach. For modeling, a template was selected by blastp at NCBI and the best template selected was 2ZW3. By comparing the template-target sequence, a model was created using MODELLER, a program for homology modeling. The accuracy of the predicted structure was checked using Ramachandran plot which showed that the residue falling in the favored region was 92.4%. The predicted GJB2 model can be used to understand the defects that lead to deafness and eventually in drug designing. Domains and different properties of GJB2 were analyzed by applying online servers. Most frequent mutations of GJB2 were discussed by differentiating between damaging and benignity.
机译:基因组测序完成了包括人类在内的数百种生物的完整遗传蓝图。在当前时代,我们试图集中精力分析,控制和修饰这些基因组编码的蛋白质的功能。这项任务是通过蛋白质的三维结构实现的。三维(3D)结构对于理解生物学功能非常有用。缝隙连接β2β(GJB2),编码缝隙连接β2α蛋白的人类基因,参与了巴基斯坦家庭的各种听力障碍。在首次报道GJB2参与巴基斯坦家庭后,有必要进一步研究这种蛋白质。因此,使用比较建模方法开发了GJB2的3D结构。对于建模,通过NCBI的blastp选择了一个模板,选择的最佳模板是2ZW3。通过比较模板目标序列,使用MODELLER(一种用于同源性建模的程序)创建了一个模型。使用Ramachandran图检查了预测结构的准确性,该图显示落入有利区域的残基为92.4%。预测的GJB2模型可用于了解导致耳聋并最终在药物设计中出现的缺陷。通过应用在线服务器来分析GJB2的域和不同属性。通过区分破坏性和良性来讨论最常见的GJB2突变。

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