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乳腺癌细胞系MCF-7凋亡途径调节因子Bcl-2基因的分子与计算研究

Molecular and Computational Studies on Apoptotic Pathway Regulator, Bcl-2 Gene from Breast Cancer Cell Line MCF-7.

作者信息

Tiwari Pragya, Khan M J

机构信息

Department of Metabolic and Structural Biology, Central Institute of Medicinal and Aromatic Plants, (CSIR-CIMAP), Lucknow-226 015, India.

Department of Biochemistry, Aligarh Muslim University, Aligarh-202 002, India.

出版信息

Indian J Pharm Sci. 2016 Jan-Feb;78(1):87-93. doi: 10.4103/0250-474x.180254.

Abstract

Cancer is a dreadful disease constituting abnormal growth and proliferation of malignant cells in the body. Next to lung cancer, breast cancer is the most common form of cancer affecting women. The apoptotic pathway regulators, B cell lymphoma family of protein, play a key role in various malignancies defining cancer and their constitutive expression plays an integral role in breast cancer chemotherapy. The research work discusses the identification and molecular cloning of a B cell lymphoma like gene from human breast cancer cell line. The open reading frame of the gene consisted of 965 nucleotides, encoding a protein of 380 amino acids with a predicted molecular weight of 42.5 kilodalton. The predicted physiochemical properties of the gene were as follows: Isoelectric point - 9.49, molecular formula - C1893H3004N534O548S16, total number of negatively charged residues, (Aspartate+Glutamate) - 26, total number of positively charged residues, (Arginine+Lysine)-39, instability index-42.08 (unstable protein) and grand average of hydropathicity is -0.202. Additionally, phobius prediction suggested non-cytoplasmic localization of the putative protein. The presence of secondary structure in the protein was determined by Memsat program. A 3 dimensional protein homology model was generated using threading based method of protein modeling for structural and functional annotation of the putative protein. Future prospects accounts for the biochemical characterization of the enzyme including in vitro assays on breast cancer cell line would establish the functional characteristics of the protein and its physiological mechanisms in breast cancer development and its therapeutic-target role in future.

摘要

癌症是一种可怕的疾病,表现为体内恶性细胞的异常生长和增殖。仅次于肺癌,乳腺癌是影响女性的最常见癌症形式。凋亡途径调节因子,即B细胞淋巴瘤蛋白家族,在定义癌症的各种恶性肿瘤中起关键作用,其组成性表达在乳腺癌化疗中起着不可或缺的作用。这项研究工作讨论了从人乳腺癌细胞系中鉴定和分子克隆一个类似B细胞淋巴瘤的基因。该基因的开放阅读框由965个核苷酸组成,编码一个由380个氨基酸组成的蛋白质,预测分子量为42.5千道尔顿。该基因预测的理化性质如下:等电点-9.49,分子式-C1893H3004N534O548S16,带负电荷残基总数(天冬氨酸+谷氨酸)-26,带正电荷残基总数(精氨酸+赖氨酸)-39,不稳定指数-42.08(不稳定蛋白),亲水性总平均值为-0.202。此外,Phobius预测表明该推定蛋白定位于非细胞质。通过Memsat程序确定该蛋白中二级结构的存在。使用基于穿线法的蛋白质建模生成三维蛋白质同源模型,用于推定蛋白的结构和功能注释。未来的前景包括对该酶进行生化表征,包括对乳腺癌细胞系进行体外测定,这将确定该蛋白的功能特性及其在乳腺癌发展中的生理机制以及其在未来的治疗靶点作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f3/4852581/35d428d46fcd/IJPhS-78-87-g001.jpg

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