新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » 癌症研究 » IUCrJ:科学家揭示抑制肝癌、结肠癌的新型分子路径

IUCrJ:科学家揭示抑制肝癌、结肠癌的新型分子路径

来源:生物谷 2014-07-10 17:21

2014年7月10日 讯 /生物谷BIOON/ --近日,刊登在国际杂志IUCrJ上的一篇研究论文中,来自西班牙、英国以及美国的研究人员通过联合研究揭示了参与肝癌和结肠癌发病过程中蛋白复合物的结构。研究者表示,仅在2012年这些类型的癌症都具有显著的社会和临床相关性,而肝癌引发的死亡率位居世界第二,结肠癌则位居第三。

文章中,来自利物浦大学等处的研究人员通过研究,成功揭示了MATα2和MATβ两种蛋白质互相结合最终促进肝癌和结肠癌肿瘤细胞再生的分子机制,该研究为研究人员后期开发特定的靶向药物来治疗癌症提供了一定的思路和希望。

研究者表示,我们可以阻断蛋白质MATα2和MATβ的独立结构,以抑制其相互结合促进癌症的发生;当其二者结合就会产生一种名为SAMe的分子,该分子在肿瘤细胞的疯狂增长过程中扮演着重要角色;尽管SAMe分子和肿瘤生长的关系在未来某个时间里会被证实,但是该分子在细胞中的其它功能却不能被改变,而且目前也没有新型途径在不影响其它机体功能的情况下抵御该分子的表达。

但幸运的是,MATα2和MATβ分子仅在成年人机体的肿瘤中处于高度表达的状态,这就为开发新型靶向疗法或者靶向药物提供了新的思路;最后研究者Adriana Rojas说道,很多年已经过去了,但是我们很庆幸我们首次揭示了产生SAMe的蛋白质分子,及SAMe分子的水平如何影响癌细胞的生长,另外蛋白质分子MATα2和MATβ之间的复杂关系也为开发治疗疾病的新型疗法提供了帮助。(生物谷Bioon.com)

Structure and function study of the complex that synthesizes S-adenosylmethionine

B. Murray, S. V. Antonyuk, A. Marina, S. M. Van Liempd, S. C. Lu, J. M. Mato, S. S. Hasnain and A. L. Rojas

S-Adenosylmethionine (SAMe) is the principal methyl donor of the cell and is synthesized via an ATP-driven process by methionine adenosyltransferase (MAT) enzymes. It is tightly linked with cell proliferation in liver and colon cancer. In humans, there are three genes, mat1A, mat2A and mat2B, which encode MAT enzymes. mat2A and mat2B transcribe MAT2 and MAT enzyme subunits, respectively, with catalytic and regulatory roles. The MAT2 complex is expressed in nearly all tissues and is thought to be essential in providing the necessary SAMe flux for methylation of DNA and various proteins including histones. In human hepatocellular carcinoma mat2A and mat2B genes are upregulated, highlighting the importance of the MAT2 complex in liver disease. The individual subunits have been structurally characterized but the nature of the complex has remained elusive despite its existence having been postulated for more than 20 years and the observation that MAT is often co-localized with MAT2. Though SAMe can be produced by MAT(2)4 alone, this paper shows that the Vmax of the MAT2 complex is three- to fourfold higher depending on the variants of MAT that participate in complex formation. Using X-ray crystallography and solution X-ray scattering, the first structures are provided of this 258 kDa functional complex both in crystals and solution with an unexpected stoichiometry of 42 and 2V2 subunits. It is demonstrated that the N-terminal regulates the activity of the complex and it is shown that complex formation takes place surprisingly via the C-terminal of MATV2 that buries itself in a tunnel created at the interface of the MAT(2)2. The structural data suggest a unique mechanism of regulation and provide a gateway for structure-based drug design in anticancer therapies.

温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库