Substrate selectivity and inhibition of histidine JmjC hydroxylases MINA53 and NO66.
Substrate selectivity and inhibition of histidine JmjC hydroxylases MINA53 and NO66.
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底物的选择性和抑制组氨酸JMJC羟化酶MINA53和NO66。
DOI：
10.1039/d2cb00182a
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发表时间：
2023-03-08
影响因子：
4.1
通讯作者：
Mecinovic, Jasmin
中科院分区：
文献类型：
--
作者：
Turkmen, Vildan A.;Hintzen, Jordi C. J.;Tumber, Anthony;Moesgaard, Laust;Salah, Eidarus;Kongsted, Jacob;Schofield, Christopher J.;Mecinovic, Jasmin
非血红素Fe（ii）和2-酮戊二酸（2 OG）依赖性加氧酶催化从细菌到人类的生物体中多种蛋白质的氧化。我们描述了对人核糖体加氧酶（ROX）MINA 53和NO 66的底物选择性和抑制的研究，MINA 53和NO 66是JmjC 2 OG加氧酶亚家族的成员，其分别催化Rpl 27 a和Rpl 8中组氨酸残基的C-3羟基化。将天然和非天然组氨酸类似物掺入Rpl肽的测定提供了证据，证明MINA 53和N 066与一些其他人JmjC羟化酶（包括抑制HIF和JMJD 6的因子）相比具有窄的底物选择性。值得注意的是，用含有具有非环状侧链的组氨酸类似物（包括Asn、Gln和homoGln）的Rpl肽进行的抑制测定的结果表明，MINA 53/N 066的活性以及由此暗示的相关20 G依赖性蛋白羟化酶/脱甲基酶的活性可能通过与非氧化蛋白/肽竞争而在体内受到调节。抑制结果也为MINA 53和NO 66选择性抑制剂的开发提供了途径。核糖体组氨酸羟化酶MINA 53和NO 66对具有组氨酸类似物的核糖体蛋白L27 a/L 8肽表现出窄的底物选择性。选择的Rpl肽显示出对MINA 53和N 066的有效抑制，为抑制剂设计提供了基础。
Non-haem Fe(ii) and 2-oxoglutarate (2OG) dependent oxygenases catalyse oxidation of multiple proteins in organisms ranging from bacteria to humans. We describe studies on the substrate selectivity and inhibition of the human ribosomal oxygenases (ROX) MINA53 and NO66, members of the JmjC 2OG oxygenase subfamily, which catalyse C-3 hydroxylation of histidine residues in Rpl27a and Rpl8, respectively. Assays with natural and unnatural histidine analogues incorporated into Rpl peptides provide evidence that MINA53 and NO66 have narrow substrate selectivities compared to some other human JmjC hydroxylases, including factor inhibiting HIF and JMJD6. Notably, the results of inhibition assays with Rpl peptides containing histidine analogues with acyclic side chains, including Asn, Gln and homoGln, suggest the activities of MINA53/NO66, and by implication related 2OG dependent protein hydroxylases/demethylases, might be regulated in vivo by competition with non-oxidised proteins/peptides. The inhibition results also provide avenues for development of inhibitors selective for MINA53 and NO66. Ribosomal histidine hydroxylases MINA53 and NO66 exhibit narrow substrate selectivities for ribosomal protein L27a/L8 peptides possessing histidine analogues. Selected Rpl peptides display potent inhibition against MINA53 and NO66, providing a basis for inhibitor design.
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影响因子：
8
作者：
Hintzen, Jordi C. J.;Ma, Huida;Deng, Hao;Witecka, Apolonia;Andersen, Steffen B.;Drozak, Jakub;Guo, Hong;Qian, Ping;Li, Haitao;Mecinovic, Jasmin
通讯作者：
Mecinovic, Jasmin
影响因子：
7.3
作者：
Nowak RP;Tumber A;Hendrix E;Ansari MSZ;Sabatino M;Antonini L;Andrijes R;Salah E;Mautone N;Pellegrini FR;Simelis K;Kawamura A;Johansson C;Passeri D;Pellicciari R;Ciogli A;Del Bufalo D;Ragno R;Coleman ML;Trisciuoglio D;Mai A;Oppermann U;Schofield CJ;Rotili D
通讯作者：
Rotili D
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML
DOI：
10.1007/s00432-009-0679-0
发表时间：
2010-03-01
影响因子：
3.6
作者：
Komiya, Kazutoshi;Sueoka-Aragane, Naoko;Sueoka, Eisaburo
通讯作者：
Sueoka, Eisaburo
影响因子：
64.8
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
通讯作者：
Schofield CJ