Structural basis for the erythro-stereospecificity of the L-arginine oxygenase VioC in viomycin biosynthesis.
Structural basis for the erythro-stereospecificity of the L-arginine oxygenase VioC in viomycin biosynthesis.
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DOI：
10.1111/j.1742-4658.2009.07085.x
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发表时间：
2009-07
期刊：
影响因子：
--
通讯作者：
Essen LO
中科院分区：
文献类型：
--
作者：
Helmetag V;Samel SA;Thomas MG;Marahiel MA;Essen LO
葡萄酒链霉菌的非血红素铁加氧酶VioC在结核放线菌素抗生素紫霉素的生物合成过程中催化L-精氨酸的Fe（II）和α-酮戊二酸依赖的Cβ-羟基化。在1.1-1.3 μ m分辨率下测定了VioC与辅因子Fe（II）、底物L-精氨酸、产物（2S，3S）-羟基精氨酸（hArg）和副产物琥珀酸盐的复合物的晶体结构。整体结构揭示了一个β-螺旋核心折叠与两个额外的螺旋子域共同的非血红素铁加氧酶的CAS样（CSL）超家族。与催化苏型非对映异构体形成的其他CAS样加氧酶不同，VioC产生Cβ-羟基化L-精氨酸的邻位非对映异构体。这种意想不到的立体特异性是由结合底物的构象控制引起的，其强制执行χ1的左（-）构象异构体，而不是天冬酰胺加氧酶AsnO和CSL超家族的其他成员观察到的反式构象异构体。此外，研究了VioC的底物特异性。L-精氨酸底物的侧链主要通过与C-末端螺旋亚结构域相互作用而从活性位点向外突出。因此，VioC通过接受类似物L-高精氨酸和L-刀豆氨酸进行Cβ-羟基化而发挥更宽的底物特异性。
The non-heme iron oxygenase VioC from Streptomyces vinaceus catalyzes Fe(II)- and α-ketoglutarate-dependent Cβ-hydroxylation of L-arginine during the biosynthesis of the tuberactinomycin antibiotic viomycin. Crystal structures of VioC were determined in complexes with the cofactor Fe(II), the substrate L-arginine, the product (2S,3S)-hydroxyarginine (hArg), and the coproduct succinate at 1.1–1.3 Å resolution. The overall structure reveals a β-helix core fold with two additional helical subdomains common to nonheme iron oxygenases of the CAS-like (CSL) superfamily. In contrast to other CAS-like oxygenases, which catalyze the formation of threo diastereomers, VioC produces the erythro diastereomer of Cβ-hydroxylated L-arginine. This unexpected stereospecificity is caused by conformational control of the bound substrate, which enforces a gauche(−) conformer for χ1 instead of the trans conformers observed for the asparagine oxygenase AsnO and other members of the CSL superfamily. Additionally, the substrate specificity of VioC was investigated. The sidechain of the L-arginine substrate projects outward from the active site by making mainly interactions with the C-terminal helical subdomain. Accordingly, VioC exerts broadened substrate specificity by accepting the analogues L-homoarginine and L-canavanine for Cβ-hydroxylation.
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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/s1744309105011565
发表时间：
2005-05-01
影响因子：
0.9
作者：
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通讯作者：
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影响因子：
8
作者：
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通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
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影响因子：
2.1
作者：
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通讯作者：
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