Discovery of proteinaceous N-modification in lysine biosynthesis of Thermus thermophilus
Discovery of proteinaceous N-modification in lysine biosynthesis of Thermus thermophilus
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DOI：
10.1038/nchembio.198
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发表时间：
2009-09-01
影响因子：
14.8
通讯作者：
Nishiyama, Makoto
中科院分区：
文献类型：
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作者：
Horie, Akira;Tomita, Takeo;Nishiyama, Makoto
虽然赖氨酸生物合成的后一部分，α-氨基己二酸（AAA）转化为赖氨酸，在嗜热栖热菌中类似于精氨酸生物合成的后一部分，但赖氨酸途径中不存在与ArgA和ArgJ同源的酶。因为已知ArgA和ArgJ修饰谷氨酸的氨基以避免中间体的分子内环化，所以它们的缺失表明该途径包括替代的N-修饰系统。我们重建了AAA向赖氨酸的转化，发现AAA的氨基通过连接到小蛋白LysW的C-末端Glu 54的γ-羧基而被修饰; AAA的侧链转化为赖氨酰侧链，同时仍然连接到LysW;赖氨酸随后从LysW-赖氨酸融合体中释放出来。生物合成酶识别LysW的酸性球状结构域的事实表明LysW充当生物合成酶的载体蛋白或蛋白支架。因此，这项研究揭示了一种小蛋白在初级代谢中以前未知的功能。
Although the latter portion of lysine biosynthesis, the conversion of alpha-aminoadipate (AAA) to lysine, in Thermus thermophilus is similar to the latter portion of arginine biosynthesis, enzymes homologous to ArgA and ArgJ are absent from the lysine pathway. Because ArgA and ArgJ are known to modify the amino group of glutamate to avoid intramolecular cyclization of intermediates, their absence suggests that the pathway includes an alternative N-modification system. We reconstituted the conversion of AAA to lysine and found that the amino group of AAA is modified by attachment to the gamma-carboxyl group of the C-terminal Glu54 of a small protein, LysW; that the side chain of AAA is converted to the lysyl side chain while still attached to LysW; and that lysine is subsequently liberated from the LysW-lysine fusion. The fact that biosynthetic enzymes recognize the acidic globular domain of LysW indicates that LysW acts as a carrier protein or protein scaffold for the biosynthetic enzymes. This study thus reveals the previously unknown function of a small protein in primary metabolism.