Structure of the ribosomal oxygenase OGFOD1 provides insights into the regio- and stereoselectivity of prolyl hydroxylases.
Structure of the ribosomal oxygenase OGFOD1 provides insights into the regio- and stereoselectivity of prolyl hydroxylases.
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DOI：
10.1016/j.str.2015.01.014
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发表时间：
2015-04-07
期刊：
影响因子：
5.7
通讯作者：
McDonough, Michael A.
中科院分区：
文献类型：
--
作者：
Horita, Shoichiro;Scotti, John S.;Thinnes, Cyrille;Mottaghi-Taromsari, Yousef S.;Thalhammer, Armin;Ge, Wei;Aik, WeiShen;Loenarz, Christoph;Schofield, Christopher J.;McDonough, Michael A.
翻译后核糖体蛋白羟基化由2-酮戊二酸（2 OG）和亚铁依赖性加氧酶催化，并发生在原核生物和真核生物中。OGFOD 1催化小核糖体亚基蛋白uS 12（RPS 23）的Pro62处的反式-3脯氨酰羟基化，并且从酵母到人类都是保守的。我们描述了人uS 12脯氨酰3-羟化酶（OGFOD 1）及其来自酿酒酵母（Saccharomycescerevisiae）的同源物（Tpa 1 p）的晶体结构：OGFOD 1与广谱2 OG加氧酶抑制剂N-草酰甘氨酸（NOG）和吡啶-2，4-二羧酸（Pyridine-2，4-dicarboxylate）复合（2，4-PDCA）分别为2.1和2.6 μ m分辨率;和Tpa 1 p与NOG、2，4-PDCA和1-氯-4-羟基异喹啉-3-羰基甘氨酸的复合物（一种选择性更强的脯氨酰羟化酶抑制剂）分别提高到2.8、1.9和1.9 μ m分辨率。uS 12羟化酶的结构与其他脯氨酰羟化酶，包括人类缺氧诱导因子（HIF）脯氨酰羟化酶（PHDs）的比较，揭示了脯氨酰3-和脯氨酰4-羟化酶活性位点之间的差异，这可以用于开发不同亚家族的选择性抑制剂。人OGFOD 1与抑制剂复合物的晶体结构。OGFOD 1和PHDs可能有共同的祖先。OGFOD 1活性位点与缺氧诱导因子脯氨酰羟化酶相当。OGFOD 1和PHD 2之间的差异可用于抑制剂设计。展示了人类第一个脯氨酰3-羟化酶OGFOD 1与小分子抑制剂复合的结构。这些结果揭示了OGFOD 1亚家族和相关的“氧敏感”缺氧诱导因子trans-P4 Hs（PHDs）的催化机制和进化。
Post-translational ribosomal protein hydroxylation is catalyzed by 2-oxoglutarate (2OG) and ferrous iron dependent oxygenases, and occurs in prokaryotes and eukaryotes. OGFOD1 catalyzes trans-3 prolyl hydroxylation at Pro62 of the small ribosomal subunit protein uS12 (RPS23) and is conserved from yeasts to humans. We describe crystal structures of the human uS12 prolyl 3-hydroxylase (OGFOD1) and its homolog from Saccharomyces cerevisiae (Tpa1p): OGFOD1 in complex with the broad-spectrum 2OG oxygenase inhibitors; N-oxalylglycine (NOG) and pyridine-2,4-dicarboxylate (2,4-PDCA) to 2.1 and 2.6 Å resolution, respectively; and Tpa1p in complex with NOG, 2,4-PDCA, and 1-chloro-4-hydroxyisoquinoline-3-carbonylglycine (a more selective prolyl hydroxylase inhibitor) to 2.8, 1.9, and 1.9 Å resolution, respectively. Comparison of uS12 hydroxylase structures with those of other prolyl hydroxylases, including the human hypoxia-inducible factor (HIF) prolyl hydroxylases (PHDs), reveals differences between the prolyl 3- and prolyl 4-hydroxylase active sites, which can be exploited for developing selective inhibitors of the different subfamilies. Crystal structures of human OGFOD1 in complex with inhibitors are presented The OGFOD1 and PHDs likely share a common ancestor The OGFOD1 active site is comparable with hypoxia-inducible factor prolyl hydroxylase Differences between OGFOD1 and PHD2 can be exploited for inhibitor design Horita et al. present structures of the first prolyl 3-hydroxylase from humans, OGFOD1, in complex with small-molecule inhibitors. The results shed light on the catalytic mechanisms and evolution of the OGFOD1 subfamily and the related “oxygen-sensing” hypoxia-inducible factor trans-P4Hs (PHDs).
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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/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
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
影响因子：
5.7
作者：
Chowdhury, Rasheduzzaman;McDonough, Michael A.;Schofield, Christopher J.
通讯作者：
Schofield, Christopher J.
影响因子：
4.8
作者：
Flashman, Emily;Bagg, Eleanor A. L.;Schofield, Christopher J.
通讯作者：
Schofield, Christopher J.