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集会自由:代谢酶聚集在一起。

Freedom of assembly: metabolic enzymes come together.

机构信息

Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111.

Department of Biochemistry, University of Washington, Seattle, Washington 98195.

出版信息

Mol Biol Cell. 2020 Jun 1;31(12):1201-1205. doi: 10.1091/mbc.E18-10-0675.

DOI:10.1091/mbc.E18-10-0675
PMID:32463766
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7353150/
Abstract

Many different enzymes in intermediate metabolism dynamically assemble filamentous polymers in cells, often in response to changes in physiological conditions. Most of the enzyme filaments known to date have only been observed in cells, but in a handful of cases structural and biochemical studies have revealed the mechanisms and consequences of assembly. In general, enzyme polymerization functions as a mechanism to allosterically tune enzyme kinetics, and it may play a physiological role in integrating metabolic signaling. Here, we highlight some principles of metabolic filaments by focusing on two well-studied examples in nucleotide biosynthesis pathways-inosine-5'-monophosphate (IMP) dehydrogenase and cytosine triphosphate (CTP) synthase.

摘要

细胞内许多不同的中间代谢酶在生理条件变化时会动态组装成丝状聚合物。到目前为止,人们所知道的大多数酶丝仅在细胞中观察到,但在少数情况下,结构和生化研究揭示了组装的机制和后果。一般来说,酶聚合作为一种变构调节酶动力学的机制,它可能在整合代谢信号中发挥生理作用。在这里,我们通过关注核苷酸生物合成途径中的两个研究较好的例子——肌苷-5'-单磷酸(IMP)脱氢酶和胞嘧啶三磷酸(CTP)合酶,强调代谢丝的一些原理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08fd/7353150/c87244947b6e/mbc-31-1201-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08fd/7353150/aea16c207b2c/mbc-31-1201-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08fd/7353150/175a1090d633/mbc-31-1201-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08fd/7353150/c87244947b6e/mbc-31-1201-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08fd/7353150/aea16c207b2c/mbc-31-1201-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08fd/7353150/175a1090d633/mbc-31-1201-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08fd/7353150/c87244947b6e/mbc-31-1201-g003.jpg

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Domain-specific AI segmentation of IMPDH2 rod/ring structures in mouse embryonic stem cells.小鼠胚胎干细胞中 IMPDH2 杆状/环状结构的特定领域人工智能分割
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本文引用的文献

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2
Cryo-EM structures demonstrate human IMPDH2 filament assembly tunes allosteric regulation.低温电子显微镜结构显示人类 IMPDH2 丝状体组装调节别构调控。
Elife. 2020 Jan 30;9:e53243. doi: 10.7554/eLife.53243.
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Coupled structural transitions enable highly cooperative regulation of human CTPS2 filaments.偶联的结构转变使人类 CTPS2 丝的高度合作调节成为可能。
Free Neuropathol. 2025 Mar 7;6:8. doi: 10.17879/freeneuropathology-2025-6282. eCollection 2025 Jan.
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Structural basis for allosteric regulation of human phosphofructokinase-1.别构调控人磷酸果糖激酶-1的结构基础。
Nat Commun. 2024 Aug 25;15(1):7323. doi: 10.1038/s41467-024-51808-6.
5
Evolutionarily divergent CTP synthase filaments are under selective pressure.进化上不同的CTP合酶丝受到选择压力。
bioRxiv. 2024 Jul 25:2024.07.25.605180. doi: 10.1101/2024.07.25.605180.
6
Two-metal ion mechanism of DNA cleavage by activated, filamentous SgrAI.被激活的、丝状 SgrAI 对 DNA 进行切割的双金属离子机制。
J Biol Chem. 2024 Aug;300(8):107576. doi: 10.1016/j.jbc.2024.107576. Epub 2024 Jul 14.
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Structural basis for allosteric regulation of human phosphofructokinase-1.人磷酸果糖激酶-1变构调节的结构基础
bioRxiv. 2024 Mar 16:2024.03.15.585110. doi: 10.1101/2024.03.15.585110.
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