Small methyltransferase RlmH assembles a composite active site to methylate a ribosomal pseudouridine.
Small methyltransferase RlmH assembles a composite active site to methylate a ribosomal pseudouridine.
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DOI：
10.1038/s41598-017-01186-5
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发表时间：
2017-04-20
影响因子：
4.6
通讯作者：
Korostelev AA
中科院分区：
文献类型：
--
作者：
Koh CS;Madireddy R;Beane TJ;Zamore PD;Korostelev AA
真细菌核糖体大亚基甲基转移酶H（RlmH）甲基化23 S核糖体RNA假尿苷1915（pseudouridine 1915），其位于核糖体解码中心附近。RlmH是甲基转移酶的SPOUT超家族中最小的成员，它缺乏在较大的甲基转移酶中发现的RNA识别结构域。RlmH酶的催化机制尚不清楚。在这里，我们描述的结构RlmH绑定到S-腺苷甲硫氨酸（SAM）和甲基转移酶抑制剂sinefungin。我们的结构和生物化学研究揭示了二聚体介导的不对称活性位点中的催化必需残基。一个单体提供SAM结合位点，而第二个单体的保守C-末端尾提供催化所必需的残基。我们的研究结果阐明了一个小的蛋白质二聚体组装一个功能不对称的架构的机制。
Eubacterial ribosomal large-subunit methyltransferase H (RlmH) methylates 23S ribosomal RNA pseudouridine 1915 (Ψ1915), which lies near the ribosomal decoding center. The smallest member of the SPOUT superfamily of methyltransferases, RlmH lacks the RNA recognition domain found in larger methyltransferases. The catalytic mechanism of RlmH enzyme is unknown. Here, we describe the structures of RlmH bound to S-adenosyl-methionine (SAM) and the methyltransferase inhibitor sinefungin. Our structural and biochemical studies reveal catalytically essential residues in the dimer-mediated asymmetrical active site. One monomer provides the SAM-binding site, whereas the conserved C-terminal tail of the second monomer provides residues essential for catalysis. Our findings elucidate the mechanism by which a small protein dimer assembles a functionally asymmetric architecture.