National Institute of Biologicals, A-32 Sector-62, Noida, U.P. India.
J Biomol Struct Dyn. 2009 Dec;27(3):283-92. doi: 10.1080/07391102.2009.10507316.
Mycobacterium tuberculosis (Mtb), the pathogen causing tuberculosis, continues to elude a cure. Latent Mtb forms are present in human population for extended periods and have the potential to be re-activated into an active form. The prophylactic vaccine, live-attenuated Mycobacterium bovis Bacillus-Calmette-Guerin (BCG) vaccine is not effective in preventing latent infection. The failure of BCG in prevention/protection against latent forms of Mtb calls for efforts to curb latent Mtb infection. The inclusion of latency/dormancy antigens in the classical antigen preparation is surmised as a strategy. DosR (Dormancy Survival Regulator, Rv3133c) regulon genes are expressed under the conditions of latency/dormancy. Previous bioinformatics analyses have pointed towards their role as probable vaccine candidates. Since nearly 60% of DosR regulon genes are unannotated, efforts towards elucidating their functional role will prove valuable. The study presented here provides an in-depth in silico 3D-structure prediction and functional analyses of the first member of the DosR regulon group, the hypothetical protein, Rv0079. A combination of approaches such as: homology modeling and threading using SWISS-MODEL workspace, Phyre and BioInfo bank Metaserver; protein localization predictions using PSORTb, LOCtree, TMHMM and TMpred; function prediction using ProFunc, epitope prediction using NetCTL and others was implemented. Evidence gathered from a combination of bioinformatics tools supports the hypothesis that Mtb Rv0079 protein is a likely cytoplasmic translation factor. Experimental validation will help provide more insight into its actual function.
结核分枝杆菌(Mtb)是导致结核病的病原体,它仍然难以治愈。潜伏的 Mtb 形式在人类中存在很长时间,并且有可能重新激活为活跃形式。预防性疫苗,减毒活牛分枝杆菌卡介苗(BCG)疫苗在预防潜伏感染方面效果不佳。BCG 在预防/保护潜伏形式的 Mtb 方面的失败,需要努力遏制潜伏 Mtb 感染。在经典抗原制剂中加入潜伏期/休眠抗原被认为是一种策略。DosR(休眠存活调节剂,Rv3133c)调控子基因在潜伏期/休眠条件下表达。以前的生物信息学分析指出它们可能是疫苗候选物。由于 DosR 调控子基因的近 60%没有注释,因此努力阐明其功能作用将是有价值的。本研究提供了对 DosR 调控子组的第一个成员,假设蛋白 Rv0079 的深入的计算机 3D 结构预测和功能分析。使用 SWISS-MODEL 工作区、Phyre 和 BioInfo bank Metaserver 进行同源建模和穿线;使用 PSORTb、LOCtree、TMHMM 和 TMpred 进行蛋白质定位预测;使用 ProFunc 进行功能预测,使用 NetCTL 和其他方法进行表位预测等多种方法的组合。从生物信息学工具组合收集的证据支持以下假设,即 Mtb Rv0079 蛋白可能是一种细胞质翻译因子。实验验证将有助于更深入地了解其实际功能。