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Nat Chem Biol:探究O-葡萄糖转移酶在癌症糖尿病等疾病中的作用

2013-05-06 Beyond 生物谷

2012年10月30日 --近日,邓迪大学研??究人员发现了人体内一种重要的酶,这种酶在癌症,老年痴呆症和糖尿病等疾病发展中起到了重要作用。 Daan van Aalten教授和他的团队一直研究细胞中的蛋白质是如何被O-葡萄糖化学修饰调节的。该团队已经证实了O-葡萄糖转移酶(OGT)是O-葡萄糖在细胞内部运作的主调节器。癌症,糖尿病和老年痴呆症等疾病中,O-葡萄糖的水平是异常的。 van Aa

2012年10月30日 --近日,邓迪大学研​​究人员发现了人体内一种重要的酶,这种酶在癌症,老年痴呆症和糖尿病等疾病发展中起到了重要作用。

Daan van Aalten教授和他的团队一直研究细胞中的蛋白质是如何被O-葡萄糖化学修饰调节的。该团队已经证实了O-葡萄糖转移酶(OGT)是O-葡萄糖在细胞内部运作的主调节器。癌症,糖尿病和老年痴呆症等疾病中,O-葡萄糖的水平是异常的。

van Aalten教授表示:对于保持细胞蛋白质处于健康状态,这种酶的反应是很重要的,一旦酶水平失调,我们就会患疾病。OGT是一个非常重要的酶,没有它,细胞是不可行的,但以前并不是真的了解该酶的运作机制。现在这项新研究揭示了这种酶是如何工作的,进而可以开发抑制剂。

虽然这种蛋白质酶对人正常功能是必不可少的,但它也在癌症,糖尿病和老年痴呆症等疾病中发挥作用,如果有一个抑制剂调整酶的活性,而不是完全删除它,这样就可以探究酶在疾病进程中的作用。
 
该研究中设计了一种抑制剂,可用于探测O-葡萄糖在这些不同疾病中的作用。例如,研究人员可以将O-葡萄糖恢复到正常水平后,分析酶是如何影响肿瘤进展的。
 
研究是由威康信托基金资助,发表在最新出版的Nature Chemical Biology杂志上。

癌症相关的拓展阅读:

O-GlcNAc transferase invokes nucleotide sugar pyrophosphate participation in catalysis

Protein O-GlcNAcylation is an essential post-translational modification on hundreds of intracellular proteins in metazoa, catalyzed by O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) using unknown mechanisms of transfer and substrate recognition. Through crystallographic snapshots and mechanism-inspired chemical probes, we define how human OGT recognizes the sugar donor and acceptor peptide and uses a new catalytic mechanism of glycosyl transfer, involving the sugar donor α-phosphate as the catalytic base as well as an essential lysine. This mechanism seems to be a unique evolutionary solution to the spatial constraints imposed by a bulky protein acceptor substrate and explains the unexpected specificity of a recently reported metabolic OGT inhibitor.

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