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首页> 外文期刊>Journal of Molecular Biology >Crystal Structure of the Pyrococcus horikoshii Isopropylmalate Isomerase Small Subunit Provides Insight into the Dual Substrate Specificity of the Enzyme.
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Crystal Structure of the Pyrococcus horikoshii Isopropylmalate Isomerase Small Subunit Provides Insight into the Dual Substrate Specificity of the Enzyme.

机译：嗜热热球菌异丙基苹果酸异丙基酯异构酶小亚基的晶体结构提供了对酶的双重底物特异性的了解。

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摘要

Recent studies have implied that the isopropylmalate isomerase small subunit of the hyperthermophilic archaea Pyrococcus horikoshii (PhIPMI-s) functions as isopropylmalate isomerase in the leucine biosynthesis pathway, and as homoaconitase (HACN) in the lysine biosynthesis pathway via alpha-aminoadipic acid. PhIPMI is thus considered a key to understanding the fundamental metabolism of the earliest organisms. We describe for the first time the crystal structure of PhIPMI-s, which displays dual substrate specificity. The crystal structure unexpectedly shows that four molecules create an interlocked assembly with intermolecular disulfide linkages having a skewed 222 point-group symmetry. Although the overall fold of the PhIPMI-s monomer is related closely to domain 4 of the aconitase (ACN), one alpha-helix in the ACN structure is replaced by a short loop with relatively high temperature factor values. Because this region is essential for discriminating the structurally similar substrate based on interactions with its diversified gamma-moiety, the loop structure in the PhIPMI-s must be dependent on the presence of a substrate. The flexibility of the loop region might be a structural basis for recognizing both hydrophobic and hydrophilic gamma-moieties of two distinct substrates, isopropylmalate and homocitrate.
机译：最近的研究表明，超嗜热古生火球菌（PIProc-s）的异丙基苹果酸异构酶小亚基在亮氨酸生物合成途径中起异丙基苹果酸异构酶的作用，并在赖氨酸生物合成途径中通过α-氨基己二酸起高醛酸酶（HACN）的作用。因此，PhIPMI被认为是了解最早生物的基本代谢的关键。我们首次描述了PhIPMI-s的晶体结构，该结构显示了双重底物特异性。晶体结构出乎意料地表明，四个分子形成了具有倾斜的222点基对称性的分子间二硫键的互锁组件。尽管PhIPMI-s单体的整体折叠与乌头酸酶（ACN）的结构域4密切相关，但ACN结构中的一个α-螺旋被具有较高温度因子值的短环取代。因为该区域对于根据与其多样化的γ-部分的相互作用来区分结构相似的底物至关重要，所以PhIPMI中的环结构必须取决于底物的存在。环状区域的柔性可能是识别两种不同底物苹果酸异丙酯和纯柠檬酸酯的疏水和亲水γ部分的结构基础。

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