杆菌有两个L-asparaginases具有低序列的相同性,但类似的结构和催化中心
Joanna I Loch1, Paulina Worsztynowicz2, Joanna Sliwiak2
1Department of Crystal Chemistry and Crystal Physics, Faculty of Chemistry, Jagiellonian University, Krakow, Poland.
Acta crystallographica. Section D, Structural biology
|July 26, 2023
概括
生乙烯编码了两个新型L-asparaginases,ReAIV和ReAV,属于新发现的第3类. 结构分析揭示了ReAIV的独特特征,尽管目前药物使用的局限性存在,但表明了酶工程的潜力.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 微生物学 微生物学
背景情况:
- 豆共生体Rhizobium etli具有两个独特的L-asparaginases,即ReAIV和ReAV. 这种共生体是豆类共生体.
- 这些酶与已知的细菌 (1类) 或植物 (2类) 的L-asparaginases没有相似之处.
- 一个假设提出ReAIV和ReAV属于一个新的结构类3.
研究的目的:
- 为了结构性地描述ReAIV,一个由Rhizobium etli.产生的构成性和热稳定的L-asparaginase.
- 将ReAIV的结构与先前解决的ReAV进行比较,以验证类3假设.
- 探索ReAIV在药物应用中的潜力,特别是作为抗白血病剂.
主要方法:
- 高分辨率的晶体结构确定ReAIV (五个结构).
- 在ReAIV和ReAV之间进行比较结构分析.
- ReAIV的生物化学特征,包括pH最佳值和基质亲和力.
主要成果:
- 晶体结构证实ReAIV是一种3类L-asparaginase,结构上与ReAV相似,但具有不同的特征.
- 关键的差异包括独特的水合模式,ReAIV中的三个内部腔,以及可变的结合位行为.
- ReAIV 呈现出高pH最佳值 (9-11) 和中度基质亲和力 (pH 9.0 时∼1.3 mM).
- 离子似乎是不可用的,Ser47可能充当催化核友.
结论:
- ReAIV代表了一个新的结构类3L-asparaginase.
- 它的结构特征,包括热稳定性和缺乏谷氨酸酶活性是有利的.
- 目前的动力学参数不适合直接使用抗白血病药物,但结构性见解可以指导未来的酶工程用于治疗应用.
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