Structures of two archaeal diphthine synthases: insights into the post-translational modification of elongation factor 2.
Structures of two archaeal diphthine synthases: insights into the post-translational modification of elongation factor 2.
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两种古菌二菲辛合酶的结构：深入了解延伸因子 2 的翻译后修饰。
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
N. Kunishima
中科院分区：
文献类型：
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作者：
S. Kishishita;K. Shimizu;K. Murayama;T. Terada;M. Shirouzu;S. Yokoyama;N. Kunishima
白喉毒素的靶点是翻译延伸因子2（EF-2）中的白喉酰胺残基，其是通过对EF-2前体中的特定组氨酸残基进行三步翻译后修饰而产生的。在第二个修饰步骤中，S-腺苷甲硫氨酸依赖性甲基转移酶，白喉合酶（DS），催化EF-2前体的三甲基化。测定了来自Pyrococcus horikoshii OT 3和Aeropyrum pernix K 1的古细菌白喉脱氢酶的同源二聚体晶体结构。这些结构与钴-前受体蛋白-4甲基转移酶CbiF基本上共有相同的总体折叠，证实DS属于二聚体III类甲基转移酶家族。在P. horikoshii DS二聚体中，两个活性位点中只有一个结合反应产物S-腺苷-L-同型半胱氨酸（S-腺苷-L-同型半胱氨酸），而另一个活性位点不含配体。这种不对称的结合可能是在两个位点中的一个位点结合后的结构域内和结构域间运动的结果。这些运动破坏了DS二聚体的双重二聚体对称性，并可能导致其他结合位点的Hcy亲和力降低。
The target of diphtheria toxin is the diphthamide residue in translation elongation factor 2 (EF-2), which is generated by a three-step post-translational modification of a specific histidine residue in the EF-2 precursor. In the second modification step, an S-adenosylmethionine-dependent methyltransferase, diphthine synthase (DS), catalyzes the trimethylation of the EF-2 precursor. The homodimeric crystal structures of the archaeal diphthine synthases from Pyrococcus horikoshii OT3 and Aeropyrum pernix K1 have been determined. These structures share essentially the same overall fold as the cobalt-precorrin-4 methyltransferase CbiF, confirming that DS belongs to the dimeric class III family of methyltransferases. In the P. horikoshii DS dimer, only one of the two active sites binds the reaction product S-adenosyl-L-homocysteine (AdoHcy), while the other active site contains no ligand. This asymmetric AdoHcy binding may be a consequence of intra-domain and inter-domain movements upon binding of AdoHcy at one of the two sites. These movements disrupt the twofold dimeric symmetry of the DS dimer and probably cause lower AdoHcy affinity at the other binding site.