GSTDTAP  > 地球科学
DOI10.1038/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
ISSN0028-0836
EISSN1476-4687
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
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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
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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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