Structure of the unusual seryl-tRNA synthetase reveals a distinct zinc-dependent mode of substrate recognition
Structure of the unusual seryl-tRNA synthetase reveals a distinct zinc-dependent mode of substrate recognition
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DOI：
10.1038/sj.emboj.7601129
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发表时间：
2006-06-07
期刊：
影响因子：
11.4
通讯作者：
Ban, Nenad
中科院分区：
文献类型：
--
作者：
Bilokapic, Silvija;Maier, Timm;Ban, Nenad
产甲烷古菌具有不寻常的丝氨酸-tRNA合成酶（SerRS），与其他古菌、真核生物和细菌中发现的SerRS在进化上不同。这两种类型的SerRS仅显示最小的序列相似性，主要在II类保守基序1、2和3内。在这里，我们报告了2.5埃分辨率的晶体结构的非典型产甲烷巴氏甲烷八叠球菌SerRS及其复合物与ATP，丝氨酸和不可水解的丝氨酰腺苷酸类似物5 '-O-（N-丝氨磺酰）腺苷。这些结构揭示了产甲烷SerRSs的两个特质特征：一个新的N-末端tRNA结合结构域和一个活性位点锌离子。四配位的Zn 2+离子与三个保守的蛋白质配体（Cys 306、Glu 355和Cys 461）结合，并结合丝氨酸底物的氨基。通过直接锌离子配体的突变分析证实了酶活性对金属离子的绝对要求。这种锌依赖性丝氨酸识别机制与细菌型SerRS所采用的机制根本不同。因此，SerRS代表了唯一已知的氨酰-tRNA合成酶系统，该系统进化出两种不同的机制来识别相同的氨基酸底物。
Methanogenic archaea possess unusual seryl-tRNA synthetase ( SerRS), evolutionarily distinct from the SerRSs found in other archaea, eucaryotes and bacteria. The two types of SerRSs show only minimal sequence similarity, primarily within class II conserved motifs 1, 2 and 3. Here, we report a 2.5 angstrom resolution crystal structure of the atypical methanogenic Methanosarcina barkeri SerRS and its complexes with ATP, serine and the non-hydrolysable seryl-adenylate analogue 5'-O-(N-serylsulfamoyl) adenosine. The structures reveal two idiosyncratic features of methanogenic SerRSs: a novel N-terminal tRNA-binding domain and an active site zinc ion. The tetra-coordinated Zn2+ ion is bound to three conserved protein ligands ( Cys306, Glu355 and Cys461) and binds the amino group of the serine substrate. The absolute requirement of the metal ion for enzymatic activity was confirmed by mutational analysis of the direct zinc ion ligands. This zinc-dependent serine recognition mechanism differs fundamentally from the one employed by the bacterial-type SerRSs. Consequently, SerRS represents the only known aminoacyl-tRNA synthetase system that evolved two distinct mechanisms for the recognition of the same amino-acid substrate.