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Structure-based Mechanistic Insights into Terminal Amide Synthase in Nosiheptide-Represented Thiopeptides Biosynthesis
其他题名硫肽nosiheptide生物合成最后一般碳酰胺化被NosA催化形成的结构研究
Liu SS(刘珊珊)1; Guo H(郭恒)1; Zhang TL(张天龙)1; Han L(韩莉)1; Me PF(么鹏飞)1; Zhang Y(张岩)1; Rong NY(荣乃燕)1; Yu Y(虞沂)1; Lan WX(蓝文贤)1; Wang CX(王春喜)1; Ding JP(丁建平)1; Wang RX(王任小)1; Liu W(刘文)1; Cao CY(曹春阳)1
2015
发表期刊Sci Rep
卷号5页码:12744
摘要Nosiheptide is a parent compound of thiopeptide family that exhibit potent activities against various bacterial pathogens. Its C-terminal amide formation is catalyzed by NosA, which is an unusual strategy for maturating certain thiopeptides by processing their precursor peptides featuring a serine extension. We here report the crystal structure of truncated NosA(1-111) variant, revealing three key elements, including basic lysine 49 (K49), acidic glutamic acid 101 (E101) and flexible C-terminal loop NosA(112-151), are crucial to the catalytic terminal amide formation in nosiheptide biosynthesis. The side-chain of residue K49 and the C-terminal loop fasten the substrate through hydrogen bonds and hydrophobic interactions. The side-chain of residue E101 enhances nucleophilic attack of H2O to the methyl imine intermediate, leading to C-alpha-N bond cleavage and nosiheptide maturation. The sequence alignment of NosA and its homologs NocA, PbtH, TpdK and BerI, and the enzymatic assay suggest that the mechanistic studies on NosA present an intriguing paradigm about how NosA family members function during thiopeptide biosynthesis.
文章类型论文
学科领域生命有机化学
DOI10.1038/srep12744
URL查看原文
收录类别SCI
语种英语
WOS记录号WOS:000359128600001
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被引频次:7[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.sioc.ac.cn/handle/331003/39517
专题生命有机化学国家重点实验室
通讯作者Liu W(刘文); Cao CY(曹春阳)
作者单位1.中科院上海有机化学研究所, 生命有机化学国家重点实验室
2.中科院上海有机化学研究所, 生物与化学交叉研究中心
3.中科院上海生命科学研究院生物化学与细胞生物学研究所
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GB/T 7714
Liu SS,Guo H,Zhang TL,et al. Structure-based Mechanistic Insights into Terminal Amide Synthase in Nosiheptide-Represented Thiopeptides Biosynthesis[J]. Sci Rep,2015,5:12744.
APA 刘珊珊.,郭恒.,张天龙.,韩莉.,么鹏飞.,...&曹春阳.(2015).Structure-based Mechanistic Insights into Terminal Amide Synthase in Nosiheptide-Represented Thiopeptides Biosynthesis.Sci Rep,5,12744.
MLA 刘珊珊,et al."Structure-based Mechanistic Insights into Terminal Amide Synthase in Nosiheptide-Represented Thiopeptides Biosynthesis".Sci Rep 5(2015):12744.
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