Ribosomal oxygenases are structurally conserved from prokaryotes to humans.
Ribosomal oxygenases are structurally conserved from prokaryotes to humans.
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DOI：
10.1038/nature13263
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发表时间：
2014-06-19
期刊：
影响因子：
64.8
通讯作者：
Schofield CJ
中科院分区：
文献类型：
--
作者：
Chowdhury R;Sekirnik R;Brissett NC;Krojer T;Ho CH;Ng SS;Clifton IJ;Ge W;Kershaw NJ;Fox GC;Muniz JRC;Vollmar M;Phillips C;Pilka ES;Kavanagh KL;von Delft F;Oppermann U;McDonough MA;Doherty AJ;Schofield CJ
2-氧戊二酸（2 OG）依赖性加氧酶通过N-甲基化染色质组分的去甲基化、转录因子和剪接因子蛋白的羟基化在基因表达的调节中起重要作用。最近，催化tRNA和核糖体蛋白的羟基化的20 G-加氧酶已被证明在与细胞生长、TH 17细胞分化和翻译准确性相关的翻译中发挥作用。核糖体加氧酶（ROX）存在于从原核生物到人类的生物体中，这一发现引发了关于它们的结构和进化关系的问题。在大肠杆菌中，ycfD催化核糖体蛋白L16中的组氨酸羟基化;在人类中，Mina 53（MYC诱导的核抗原）和NO 66（核仁蛋白66）分别催化核糖体蛋白rpL 27 a和rpL 8中的组氨酸羟基化。ROX的功能分配打开了通过ROX抑制或靶向差异修饰的核糖体的治疗可能性。尽管原核和真核ROX的残基和蛋白质选择性不同，但来自E. coli和Rhodothermus marinus与人Mina 53和NO 66（hROX）的结构相似，揭示了高度保守的折叠和新的二聚模式，定义了一个新的2 OG-加氧酶亚家族。ROX结构与/不与其底物复合，支持其作为羟化酶的功能分配，但不是脱甲基酶，并揭示了该亚家族如何进化以催化核糖体蛋白的不同残基侧链的羟基化。ROX晶体结构与其他JmjC-羟化酶包括缺氧诱导因子天冬酰胺酰羟化酶（FIH）和组蛋白Nε-甲基赖氨酸脱甲基酶（KDM）的晶体结构的比较确定了2 OG-加氧酶进化中的分支点，并区分了JmjC-羟化酶和催化翻译和转录机制修饰的-脱甲基酶。结构表明，新的蛋白质羟基化活性可以通过改变铁结合的底物氧化物种反应的配位位置来进化。这种配位灵活性可能有助于铁加氧酶催化的广泛反应的演变。
2-Oxoglutarate (2OG)-dependent oxygenases play important roles in the regulation of gene expression via demethylation of N-methylated chromatin components, hydroxylation of transcription factors, and of splicing factor proteins. Recently, 2OG-oxygenases that catalyze hydroxylation of tRNA and ribosomal proteins, have been shown to play roles in translation relating to cellular growth, TH17-cell differentiation and translational accuracy. The finding that the ribosomal oxygenases (ROX) occur in organisms ranging from prokaryotes to humans raises questions as to their structural and evolutionary relationships. In Escherichia coli, ycfD catalyzes arginine-hydroxylation in the ribosomal protein L16; in humans, Mina53 (MYC-induced nuclear antigen) and NO66 (Nucleolar protein 66) catalyze histidine-hydroxylation in ribosomal proteins rpL27a and rpL8, respectively. The functional assignments of the ROX open therapeutic possibilities via either ROX inhibition or targeting of differentially modified ribosomes. Despite differences in residue- and protein-selectivities of prokaryotic and eukaryotic ROX, crystal structures of ycfD and ycfDRM from E. coli and Rhodothermus marinus with those of human Mina53 and NO66 (hROX) reveal highly conserved folds and novel dimerization modes defining a new structural subfamily of 2OG-oxygenases. ROX structures in complex with/without their substrates, support their functional assignments as hydroxylases, but not demethylases and reveal how the subfamily has evolved to catalyze the hydroxylation of different residue sidechains of ribosomal proteins. Comparison of ROX crystal structures with those of other JmjC-hydroxylases including the hypoxia-inducible factor asparaginyl-hydroxylase (FIH) and histone Nε-methyl lysine demethylases (KDMs) identifies branchpoints in 2OG-oxygenase evolution and distinguishes between JmjC-hydroxylases and -demethylases catalyzing modifications of translational and transcriptional machinery. The structures reveal that new protein hydroxylation activities can evolve by changing the coordination position from which the iron-bound substrate oxidizing species reacts. This coordination flexibility has likely contributed to the evolution of the wide range of reactions catalyzed by iron-oxygenases.
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影响因子：
4.8
作者：
Elkins, JM;Hewitson, KS;Schofield, CJ
通讯作者：
Schofield, CJ
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL
影响因子：
5.8
作者：
Bond, CS
通讯作者：
Bond, CS
影响因子：
5.3
作者：
Del Rizzo, Paul A.;Krishnan, Swathi;Trievel, Raymond C.
通讯作者：
Trievel, Raymond C.