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DOI | 10.1038/nature23285 |
Low-barrier hydrogen bonds in enzyme cooperativity | |
Dai, Shaobo1,2,3; Funk, Lisa-Marie1,2,3; von Pappenheim, Fabian Rabe1,2,3; Sautner, Viktor1,2,3; Paulikat, Mirko4; Schroder, Benjamin4; Uranga, Jon4; Mata, Ricardo A.4; Tittmann, Kai1,2,3 | |
2019-09-26 | |
发表期刊 | NATURE
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ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2019 |
卷号 | 573期号:7775页码:609-+ |
文章类型 | Article |
语种 | 英语 |
国家 | Germany |
英文摘要 | The underlying molecular mechanisms of cooperativity and allosteric regulation are well understood for many proteins, with haemoglobin and aspartate transcarbamoylase serving as prototypical examples(1,2). The binding of effectors typically causes a structural transition of the protein that is propagated through signalling pathways to remote sites and involves marked changes on the tertiary and sometimes even the quaternary level(1-5). However, the origin of these signals and the molecular mechanism of long-range signalling at an atomic level remain unclear(5-8). The different spatial scales and timescales in signalling pathways render experimental observation challenging; in particular, the positions and movement of mobile protons cannot be visualized by current methods of structural analysis. Here we report the experimental observation of fluctuating low-barrier hydrogen bonds as switching elements in cooperativity pathways of multimeric enzymes. We have observed these low-barrier hydrogen bonds in ultra-high-resolution X-ray crystallographic structures of two multimeric enzymes, and have validated their assignment using computational calculations. Catalytic events at the active sites switch between low-barrier hydrogen bonds and ordinary hydrogen bonds in a circuit that consists of acidic side chains and water molecules, transmitting a signal through the collective repositioning of protons by behaving as an atomistic Newton's cradle. The resulting communication synchronizes catalysis in the oligomer. Our studies provide several lines of evidence and a working model for not only the existence of low-barrier hydrogen bonds in proteins, but also a connection to enzyme cooperativity. This finding suggests new principles of drug and enzyme design, in which sequences of residues can be purposefully included to enable long-range communication and thus the regulation of engineered biomolecules. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000488247600064 |
WOS关键词 | COUPLED ELECTRON-TRANSFER ; THIAMIN DIPHOSPHATE ; PYRUVATE OXIDASE ; BASIS-SETS ; SITES REACTIVITY ; E1 COMPONENT ; ACTIVE-SITE ; TRANSKETOLASE ; CATALYSIS ; PROTON |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/202763 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Georg August Univ Gottingen, Gottingen Ctr Mol Biosci, Dept Mol Enzymol, Gottingen, Germany; 2.Georg August Univ Gottingen, Albrecht von Haller Inst, Gottingen, Germany; 3.Max Planck Inst Biophys Chem Gottingen, Dept Struct Dynam, Gottingen, Germany; 4.Georg August Univ Gottingen, Inst Phys Chem, Gottingen, Germany |
推荐引用方式 GB/T 7714 | Dai, Shaobo,Funk, Lisa-Marie,von Pappenheim, Fabian Rabe,et al. Low-barrier hydrogen bonds in enzyme cooperativity[J]. NATURE,2019,573(7775):609-+. |
APA | Dai, Shaobo.,Funk, Lisa-Marie.,von Pappenheim, Fabian Rabe.,Sautner, Viktor.,Paulikat, Mirko.,...&Tittmann, Kai.(2019).Low-barrier hydrogen bonds in enzyme cooperativity.NATURE,573(7775),609-+. |
MLA | Dai, Shaobo,et al."Low-barrier hydrogen bonds in enzyme cooperativity".NATURE 573.7775(2019):609-+. |
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