菌根酶对变异原体进行选择性去胺
1Department of Chemistry, Indian Institute of Technology Bombay , Powai, Mumbai 400076, India.
Journal of the American Chemical Society
|July 15, 2017
概括
研究人员在Mycobacterium物种中发现了一种新的酶类, 酶Msd对突变基进行校对, 具有治疗潜力.
科学领域:
- 生物化学
- 结构生物学
- 酵素学
背景情况:
- 基于结构的方法对于发现新的治疗功能至关重要.
- 菌根菌种含有高密度的除氨酶,这表明它们具有独特的代谢作用.
研究的目的:
- 发现和描述一种来自Mycobacterium物种的新类除氨酶.
- 阐明一种新型除氨酶Msd的基质特异性和结构基础.
- 了解突变原体识别的机制以及酶在异生物耐药性中的作用.
主要方法:
- 酶净化和生物化学测试
- 在1.9 Å分辨率下测定酶结构的X射线晶体.
- 分析酶基质与三类同类的相互作用.
主要成果:
- 鉴定了一种对s-triazine化合物起作用的新型除氨酶.
- 来自Mycobacterium smegmatis的MSD特异性去胺基基 (5-azacytosine,isoguanine),但不是天然基.
- Msd 的活性位点是混合细胞素-氨酸脱氨酶,可容纳素和胺类突变原体.
- 结构分析揭示了MSD对变异原体的校对机制.
结论:
- Msd 是一种具有混合活性位点的独特除氨酶类,其基质范围扩大到可能有害的变异原体.
- 该酶的基因组位置表明它在通过排泄机制对外源生物的天生的耐药性中起作用.
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