来自Mycobacterium tuberculosis的结核醇合成酶和脱烯二酸盐合成酶的结构和抑制
Hsiu-Chien Chan1, Xinxin Feng, Tzu-Ping Ko
1Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology , Tianjin 300308, China.
Journal of the American Chemical Society
|January 31, 2014
概括
研究人员阐明了Mycobacterium tuberculosis中关键酶Rv3378c的结构,揭示了其独特的机制. 这一发现可能会导致针对细菌毒性和细胞壁生物合成的新型抗感染疗法.
科学领域:
- 结构生物学是结构生物学.
- 生物化学 生物化学
- 药物发现 药物发现
背景情况:
- 结核菌菌是一种病原体,需要新的抗感染策略.
- 细菌的二二烯合成酶在毒性因子形成中起作用.
- Rv3378c是阻止毒性的一种潜在药物标.
研究的目的:
- 确定Rv3378c的结构,这是一种来自Mycobacterium tuberculosis的细菌二烯合成酶.
- 为了阐明Rv3378c.的作用机制.
- 为开发新的抗感染剂提供结构性见解.
主要方法:
- 通过X射线晶体学,获得了Rv3378c.的结构.
- 仅对酶,基质和抑制剂来确定结构.
- 用局部导向的突变发生法来研究酶机制.
主要成果:
- 确定了Rv3378c的结构,揭示了类似于prenyltransferases的折叠.
- 具有基质和抑制剂的结构为结合和抑制机制提供了洞察力.
- 有证据表明,一种不寻常的催化机制涉及两个氨酸残留物.
结论:
- Rv3378c与M.结核病的cis-decaprenyl diphosphate synthase (DPPS) 具有结构和功能上的相似之处.
- 结构数据和机械洞察力可以指导双作用抑制剂的开发.
- 这些抑制剂可以针对细菌毒性和细胞壁生物合成.
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