Conservation of the unusual dimeric JmjC fold of JMJD7 from Drosophila melanogaster to humans.

Conservation of the unusual dimeric JmjC fold of JMJD7 from Drosophila melanogaster to humans.
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果蝇JMJD7不寻常的二聚体JmjC折叠对人类的保护。

DOI:
10.1038/s41598-022-10028-y
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发表时间:
2022-04-11
期刊:
影响因子:
4.6
通讯作者:
Schofield, Christopher J.
Schofield, Christopher J.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chowdhury, Rasheduzzaman;Abboud, Martine, I;Wiley, James;Tumber, Anthony;Markolovic, Suzana;Schofield, Christopher J.

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2-酮戊二酸依赖性加氧酶的JmjC家族催化人类和其他动物中的一系列羟基化和去甲基化反应。含Jumonji结构域7(JMJD 7)是一种JmjC(3S)-赖氨酰羟化酶,可催化发育调节GTP结合蛋白1和2(DRG 1和2)的修饰; JMJD 7也被报道具有组蛋白内肽酶活性。在这里,我们报告的生物物理和生物化学研究JMJD 7从果蝇(dmJMJD 7)。值得注意的是,晶体学分析表明,JMJD 7不寻常的二聚化模式在人JMJD 7(hsJMJD 7)中是保守的,该模式涉及两个dmJMJD 7单体的N末端和C末端区域之间的相互作用以及二硫键的形成。结果进一步支持JMJD 7作为赖氨酰羟化酶的分配,并将有助于开发其和其他JmjC加氧酶的选择性抑制剂。
The JmjC family of 2-oxoglutarate dependent oxygenases catalyse a range of hydroxylation and demethylation reactions in humans and other animals. Jumonji domain-containing 7 (JMJD7) is a JmjC (3S)-lysyl-hydroxylase that catalyses the modification of Developmentally Regulated GTP Binding Proteins 1 and 2 (DRG1 and 2); JMJD7 has also been reported to have histone endopeptidase activity. Here we report biophysical and biochemical studies on JMJD7 from Drosophila melanogaster (dmJMJD7). Notably, crystallographic analyses reveal that the unusual dimerization mode of JMJD7, which involves interactions between both the N- and C-terminal regions of both dmJMJD7 monomers and disulfide formation, is conserved in human JMJD7 (hsJMJD7). The results further support the assignment of JMJD7 as a lysyl hydroxylase and will help enable the development of selective inhibitors for it and other JmjC oxygenases.
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