通过使用结构和基因组背景来发现新的酶和代谢途径
Suwen Zhao1, Ritesh Kumar, Ayano Sakai
11] Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143, USA [2].
Nature
|September 24, 2013
概括
这项研究使用计算代谢物对接和途径背景来准确预测酶功能,并确定细菌中的新代谢途径. 这种结构导向的方法克服了蛋白质功能分配的挑战,并有助于发现新的生物过程.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 基因组学就是基因组学.
背景情况:
- 从基因组项目中分配蛋白质功能是困难的,因为过度预测和注释错误.
- 包括代谢物对接在内的计算策略正在开发中,用于使用蛋白质结构进行功能发现.
- 细菌的代谢途径通常存在于基因集群中,为功能分配提供了背景.
研究的目的:
- 证明结构导向方法对预测酶基质特异性和代谢途径的有用性.
- 正确识别以前未被描述的酶的功能和途径 (PDB 2PMQ).
- 为了证实trans-4-hydroxy-L-proline贝他因 (tHyp-B) 的溶解作用.
主要方法:
- 代谢物对接到蛋白质结构 (3D) 以预测基质特异性.
- 分析细菌基因集群和路径背景.
- 在体外酶分析,遗传分析,代谢学和转录学.
主要成果:
- 准确地预测了tHyp-B和cHyp-B的2-epimerization由具有PDB 2PMQ的酶.
- 正确识别了涉及Hyp-B 2-epimerase的代谢途径.
- 通过多种实验方法确认了酶活性,确定了途径中间体,并通过多种实验方法确定了tHyp-B的溶解作用.
结论:
- 结构导向的功能预测,结合途径上下文,对于发现新的代谢途径是有效的.
- 代谢物对接提高了预测酶基质特异性的可靠性.
- 这种方法验证了未表征的蛋白质的功能,并阐明了新的生物学途径.
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