Crystal Structure of Human Nocturnin Catalytic Domain.
Crystal Structure of Human Nocturnin Catalytic Domain.
复制标题
DOI：
10.1038/s41598-018-34615-0
复制
发表时间：
2018-11-02
影响因子：
4.6
通讯作者：
Korennykh A
中科院分区：
文献类型：
--
作者：
Estrella MA;Du J;Korennykh A
Nocturnin（NOCT）帮助生物钟根据昼夜活动调整新陈代谢。NOCT在傍晚上调，并且已经提出NOCT充当代谢酶mRNA的去腺苷酶。我们提出了一个2.7-ε晶体结构的催化域的人NOCT。我们的结构表明，NOCT有一个密切的整体相似性，CCR 4 deadenylase家族成员，PDE 12和hocT 6L，和DNA修复酶TDP 2。PDE 12、hocT 6L和TDP 2中存在的所有关键催化残基在NOCT中是保守的，并且具有相同的构象。然而，我们观察到NOCT，一个意想不到的狭窄的活性位点口袋，和保守的结构元件的催化中心，这是独特的NOCT和不存在的deadenylases PDE 12/hocT 6L附近的表面性质的实质性差异。此外，我们表明，与人PDE 12和hocT 6L相反，NOCT对poly-A RNA完全无活性。因此，我们的工作揭示了一个有趣的昼夜节律蛋白的结构，并表明NOCT与相关的去腺苷酸酶有相当大的差异，这可能表明这种酶具有独特的细胞功能。
Nocturnin (NOCT) helps the circadian clock to adjust metabolism according to day and night activity. NOCT is upregulated in early evening and it has been proposed that NOCT serves as a deadenylase for metabolic enzyme mRNAs. We present a 2.7-Å crystal structure of the catalytic domain of human NOCT. Our structure shows that NOCT has a close overall similarity to CCR4 deadenylase family members, PDE12 and CNOT6L, and to a DNA repair enzyme TDP2. All the key catalytic residues present in PDE12, CNOT6L and TDP2 are conserved in NOCT and have the same conformations. However, we observe substantial differences in the surface properties of NOCT, an unexpectedly narrow active site pocket, and conserved structural elements in the vicinity of the catalytic center, which are unique to NOCT and absent in the deadenylases PDE12/CNOT6L. Moreover, we show that in contrast to human PDE12 and CNOT6L, NOCT is completely inactive against poly-A RNA. Our work thus reveals the structure of an intriguing circadian protein and suggests that NOCT has considerable differences from the related deadenylases, which may point to a unique cellular function of this enzyme.
登录
查看更多内容
影响因子：
16.8
作者：
Freudenthal BD;Beard WA;Cuneo MJ;Dyrkheeva NS;Wilson SH
通讯作者：
Wilson SH
影响因子：
14.9
作者：
Abshire ET;Chasseur J;Bohn JA;Del Rizzo PA;Freddolino PL;Goldstrohm AC;Trievel RC
通讯作者：
Trievel RC
影响因子：
7.7
作者：
Pearce, Sarah F.;Rorbach, Joanna;Minczuk, Michal
通讯作者：
Minczuk, Michal
影响因子：
3
作者：
Pettersen, EF;Goddard, TD;Ferrin, TE
通讯作者：
Ferrin, TE
影响因子：
9.2
作者：
Baggs, JE;Green, CB
通讯作者：
Green, CB