Structural insight into concerted inhibition of α2β2-type aspartate kinase from Corynebacterium glutamicum
Structural insight into concerted inhibition of α2β2-type aspartate kinase from Corynebacterium glutamicum
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DOI：
10.1016/j.jmb.2007.02.017
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发表时间：
2007-04-27
影响因子：
5.6
通讯作者：
Nishiyama, Makoto
中科院分区：
文献类型：
--
作者：
Yoshida, Ayako;Tomita, Takeo;Nishiyama, Makoto
天冬氨酸激酶（AK）催化天冬氨酸家族氨基酸生物合成的第一步，并且通过包括Thr和Lys的终产物的反馈抑制来调节。为了阐明这种抑制的机制，我们以1.58埃的分辨率测定了谷氨酸棒杆菌AK调节亚基的晶体结构，其为Th结合形式，即α 2 β 2型AK调节亚基的第一种晶体结构。调节亚基每个单体含有两个ACT结构域基序，并排列为二聚体。来自不同链的两个非等效ACT结构域形成结合单个Thr分子的效应子结合单元，并且所得的二聚体的两个效应子结合单元以面对面的方式垂直缔合。调节亚基在没有Thr的情况下是单体，但通过加入Thr而变成二聚体。突变型AK的Thr结合区发生改变后，二聚化被消除，提示Thr结合诱导的二聚化是C.谷氨酸。本文还讨论了CgAK的一个可能的赖氨酸结合位点及其抑制机制。(c)2007爱思唯尔有限公司保留所有权利。
Aspartate kinase (AK) catalyzes the first step of the biosynthesis of the aspartic acid family amino acids, and is regulated via feedback inhibition by end-products including Thr and Lys. To elucidate the mechanism of this inhibition, we determined the crystal structure of the regulatory subunit of AK from Corynebacterium glutamicum at 1.58 angstrom resolution in the Thr-binding form, the first crystal structure of the regulatory subunit Of alpha(2)beta(2)-type AK. The regulatory subunit contains two ACT domain motifs per monomer and is arranged as a dimer. Two non-equivalent ACT domains from different chains form an effector-binding unit that binds a single Thr molecule, and the resulting two effector-binding units of the dimer associate perpendicularly in a face-to-face manner. The regulatory subunit is a monomer in the absence of Thr but becomes a dimer by adding Thr. The dimerization is eliminated in mutant AKs with changes in the Thr-binding region, suggesting that the dimerization induced by Thr binding is a key step in the inhibitory mechanism of AK from C. glutamicum. A putative Lysbinding site and the inhibitory mechanism of CgAK are discussed. (c) 2007 Elsevier Ltd. All rights reserved.