结核分枝杆菌天冬氨酸激酶调节亚基的结构视图。
Structural view of the regulatory subunit of aspartate kinase from Mycobacterium tuberculosis.
机构信息
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
出版信息
Protein Cell. 2011 Sep;2(9):745-54. doi: 10.1007/s13238-011-1094-2. Epub 2011 Oct 6.
Abstract
The aspartate kinase (AK) from Mycobacterium tuberculosis (Mtb) catalyzes the biosynthesis of aspartate family amino acids, including lysine, threonine, isoleucine and methionine. We determined the crystal structures of the regulatory subunit of aspartate kinase from Mtb alone (referred to as MtbAKβ) and in complex with threonine (referred to as MtbAKβ-Thr) at resolutions of 2.6 Å and 2.0 Å, respectively. MtbAKβ is composed of two perpendicular non-equivalent ACT domains [aspartate kinase, chorismate mutase, and TyrA (prephenate dehydrogenase)] per monomer. Each ACT domain contains two α helices and four antiparallel β strands. The structure of MtbAKβ shares high similarity with the regulatory subunit of the aspartate kinase from Corynebacterium glutamicum (referred to as CgAKβ), suggesting similar regulatory mechanisms. Biochemical assays in our study showed that MtbAK is inhibited by threonine. Based on crystal structure analysis, we discuss the regulatory mechanism of MtbAK.
摘要
结核分枝杆菌（Mtb）天冬氨酸激酶（AK）催化天冬氨酸族氨基酸的生物合成，包括赖氨酸、苏氨酸、异亮氨酸和蛋氨酸。我们分别解析了 MtbAK 调节亚基与苏氨酸结合（MtbAKβ-Thr）和游离状态（MtbAKβ）的晶体结构，分辨率分别为 2.6 Å 和 2.0 Å。MtbAKβ 由每个单体中的两个垂直非等价的 ACT 结构域（天冬氨酸激酶、分支酸变位酶和 TyrA（预苯酸脱氢酶））组成。每个 ACT 结构域包含两个α螺旋和四个反平行β链。MtbAKβ 的结构与谷氨酸棒状杆菌的天冬氨酸激酶的调节亚基（CgAKβ）高度相似，表明存在相似的调节机制。我们的生化实验表明 MtbAK 受到苏氨酸的抑制。基于晶体结构分析，我们讨论了 MtbAK 的调节机制。
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本文引用的文献
1
Processing of X-ray diffraction data collected in oscillation mode.振荡模式下收集的X射线衍射数据的处理。
Methods Enzymol. 1997;276:307-26. doi: 10.1016/S0076-6879(97)76066-X.
2
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Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Mar 1;67(Pt 3):380-5. doi: 10.1107/S1744309111000030. Epub 2011 Feb 25.
3
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J Biol Chem. 2010 Aug 27;285(35):27477-27486. doi: 10.1074/jbc.M110.111153. Epub 2010 Jun 23.
4
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5
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Phaser crystallographic software.相位结晶学软件。
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674. doi: 10.1107/S0021889807021206. Epub 2007 Jul 13.
8
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Curr Opin Infect Dis. 2008 Dec;21(6):587-95. doi: 10.1097/QCO.0b013e328319bce6.
9
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