人类peptidylarginine deiminase类型VI (PAD6) 的晶体结构为其不活性提供了洞察力
Fanomezana M Ranaivoson1, Rieke Bande2, Isabell Cardaun3
1Protein Sciences Department, Evotec (United Kingdom), 95 Park Drive, Abingdon OX14 4RY, United Kingdom.
IUCrJ
|April 24, 2024
概括
人类peptidylarginine deiminase异型VI (PAD6) 对于女性生育至关重要. 它的晶体结构显示出一个不活跃的构造,这表明它在卵细胞中发挥了非酶作用或是一种新的激活机制.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 生殖生物学 生殖生物学
背景情况:
- 人类丁氨酸减弱酶异型VI (PAD6) 对于女性生育至关重要,并且局部存在卵细胞细胞质格子中.
- PAD6是丁氨酸脱酶 (PAD) 酶家族的一部分,催化氨酸转化为氨酸.
- 之前的研究表明,重组PAD6具有催化不活性,这促使进行结构性研究.
研究的目的:
- 阐明PAD6观察到的催化不活性的结构基础.
- 为人类PAD6在卵细胞中的功能提供结构性见解.
主要方法:
- 进行X射线晶体学以确定PAD6.6的1.7 Å分辨率结构.
- 尺寸排除色谱和差异扫描度学用于生物化学分析.
- 将PAD6结构与其他PAD异酶的结构进行比较.
主要成果:
- 确定了人类PAD6的第一个晶体结构,揭示了与其他PAD相似的域组织.
- PAD6形成一个同极体,并且不协调Ca2+.
- 活性部位采用非生产性构造,阻碍基质结合和催化活性,与观察到的不活性相一致.
结论:
- PAD6的非活性构造表明在卵细胞细胞质晶格内具有非酶功能.
- 另外,PAD6可能需要一个独特的激活机制,与其他PAD酶不同.
- 结构性发现为了解PAD6在女性生育能力中的作用提供了基础.
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