Biochemical, structural and cellular studies reveal Jumonji-C (JmjC) domain-containing 7 (JMJD7) to be a 2-oxoglutarate (2OG)-dependent oxygenase that catalyzes (3S)-lysyl hydroxylation. Crystallographic analyses reveal JMJD7 to be more closely related to the JmjC hydroxylases than to the JmjC demethylases. Biophysical and mutation studies show that JMJD7 has a unique dimerization mode, with interactions between monomers involving both N- and C-terminal regions and disulfide bond formation. A proteomic approach identifies two related members of the translation factor (TRAFAC) family of GTPases, developmentally regulated GTP-binding proteins 1 and 2 (DRG1/2), as activity-dependent JMJD7 interactors. Mass spectrometric analyses demonstrate that JMJD7 catalyzes Fe(II)- and 2OG-dependent hydroxylation of a highly conserved lysine residue in DRG1/2; amino-acid analyses reveal that JMJD7 catalyzes (3S)-lysyl hydroxylation. The functional assignment of JMJD7 will enable future studies to define the role of DRG hydroxylation in cell growth and disease.

中文翻译：

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Jumonji-C 加氧酶 JMJD7 催化 TRAFAC GTP 酶的 (3S)-赖氨酰羟基化。


生化、结构和细胞研究表明，含有 Jumonji-C (JmjC) 结构域的 7 (JMJD7) 是一种 2-酮戊二酸 (2OG) 依赖性加氧酶，可催化 (3S)-赖氨酰羟基化。晶体学分析表明，JMJD7 与 JmjC 羟化酶的关系比与 JmjC 脱甲基酶的关系更密切。生物物理和突变研究表明，JMJD7 具有独特的二聚化模式，单体之间的相互作用涉及 N 端和 C 端区域以及二硫键的形成。蛋白质组学方法鉴定了 GTP 酶翻译因子 (TRAFAC) 家族的两个相关成员，即发育调节的 GTP 结合蛋白 1 和 2 (DRG1/2)，作为活性依赖性 JMJD7 相互作用蛋白。质谱分析表明，JMJD7 催化 DRG1/2 中高度保守的赖氨酸残基的 Fe(II) 和 2OG 依赖性羟基化；氨基酸分析表明，JMJD7 催化 (3S)-赖氨酰羟基化。 JMJD7 的功能分配将使未来的研究能够确定 DRG 羟基化在细胞生长和疾病中的作用。