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来自Cryptococcus neoformans的3-二氨酸降解酶TSC10的晶体结构

Panqi Zhao¹, Zewen Zhuang¹, Xueyan Guan¹

¹Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China; Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangzhou, 510632, China; Guangdong Provincial Biotechnology Drug & Engineering Technology Research Center, Guangzhou, 510632, China; National Engineering Research Center of Genetic Medicine, Guangzhou, 510632, China.

Biochemical and biophysical research communications

|June 7, 2023

概括

确定了真菌3-ketodihydrosphingosine减少酶 (KDSR) 的晶体结构,揭示了一个灵活的催化部位. 这种结构可能能够选择性抑制真菌KDSR二分化.

科学领域:

生物化学生化学
结构生物学结构生物学
菌类学菌类学是指菌类学.

背景情况:

脂生物合成对于细胞功能至关重要.
3-二氨酸减少酶 (KDSR) 催化了一个关键的减少步骤.
以前没有KDSR酶的实验结构可用.

研究的目的:

确定真菌3-二氨酸减少酶 (TSC10) 的催化域的晶体结构.
研究KDSR功能的结构基础和选择性抑制的潜力.

主要方法:

使用X射线晶体学来确定与NADPH复合的Cryptococcus neoformans TSC10 (cnTSC10) 的结构.
进行了生物信息分析和与哺乳动物KDSR (FVT-1) 的比较.

主要成果:

cnTSC10催化域的晶体结构揭示了在催化部位具有显著灵活性的罗斯曼折叠.
cnTSC10主要以溶液中的二元体的形式存在,并确定了特定的接口.
在真菌和哺乳动物KDSR之间,二聚体接口的关键残留物没有保存.

结论:

确定的cnTSC10结构为脂生物合成和酶灵活性提供了洞察力.
在二聚体界面缺乏保存的残留物为开发选择性抗真菌抑制剂提供了潜在的策略.

关键词:

3 - 基托二二松氨酸减少酶.这是Cryptococcus neoformans的新型菌.晶体结构晶体结构这就是KDSRR.这是TSC10的TSC10.

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