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在晶体中可视化并鉴定肌醇焦磷酸异构体

Visualizing and Identifying Inositol Pyrophosphate Isomers in Crystallo.

作者信息

Zong Guangning, Wang Huanchen

机构信息

Genomic Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.

Molecular and Cellular Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.

出版信息

Methods Mol Biol. 2025;2972:189-203. doi: 10.1007/978-1-0716-4799-8_14.

DOI:10.1007/978-1-0716-4799-8_14
PMID:40879987
Abstract

Inositol pyrophosphates (PP-InsPs), which possess functionally significant diphosphate groups, regulate a wide range of biological processes across eukaryotic organisms. The presence and isomeric diversity of PP-InsPs suggest potential biological relevance and enable these molecules to serve as versatile regulators. Identification and characterization of the PP-InsP isomers require specialized approaches. We have successfully utilized X-ray crystallography to directly visualize and identify PP-InsP isomers, thereby informing biological studies and advancing our understanding of their functional roles. Here, we describe detailed methods for identifying PP-InsP isomers in Crystallo.

摘要

肌醇焦磷酸(PP-InsPs)含有具有重要功能的二磷酸基团,可调节真核生物中的多种生物过程。PP-InsPs的存在及其异构体多样性表明其具有潜在的生物学相关性,并使这些分子能够作为多功能调节剂发挥作用。PP-InsP异构体的鉴定和表征需要专门的方法。我们已成功利用X射线晶体学直接可视化和鉴定PP-InsP异构体,从而为生物学研究提供信息并增进我们对其功能作用的理解。在此,我们描述了在晶体中鉴定PP-InsP异构体的详细方法。

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本文引用的文献

1
Inositol Pyrophosphates as Versatile Metabolic Messengers.肌醇焦磷酸作为多功能代谢信使。
Annu Rev Biochem. 2024 Aug;93(1):317-338. doi: 10.1146/annurev-biochem-030222-121901.
2
Homeostatic coordination of cellular phosphate uptake and efflux requires an organelle-based receptor for the inositol pyrophosphate IP8.细胞内磷酸盐摄取和外排的动态协调需要一种基于细胞器的肌醇六磷酸 IP8 受体。
Cell Rep. 2024 Jun 25;43(6):114316. doi: 10.1016/j.celrep.2024.114316. Epub 2024 Jun 2.
3
Biochemical and structural characterization of an inositol pyrophosphate kinase from a giant virus.
一种巨型病毒肌醇六磷酸激酶的生化和结构特征。
EMBO J. 2024 Feb;43(3):462-480. doi: 10.1038/s44318-023-00005-0. Epub 2024 Jan 12.
4
IP8: A quantitatively minor inositol pyrophosphate signaling molecule that punches above its weight.IP8:一种数量较少但具有重要作用的肌醇焦磷酸盐信号分子。
Adv Biol Regul. 2024 Jan;91:101002. doi: 10.1016/j.jbior.2023.101002. Epub 2023 Dec 1.
5
Fluorination Influences the Bioisostery of Myo-Inositol Pyrophosphate Analogs.氟原子取代对肌醇六磷酸类似物的生物等排性的影响。
Chemistry. 2023 Dec 1;29(67):e202302426. doi: 10.1002/chem.202302426. Epub 2023 Oct 19.
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Capillary electrophoresis mass spectrometry identifies new isomers of inositol pyrophosphates in mammalian tissues.毛细管电泳质谱法鉴定哺乳动物组织中肌醇焦磷酸的新异构体。
Chem Sci. 2022 Dec 5;14(3):658-667. doi: 10.1039/d2sc05147h. eCollection 2023 Jan 18.
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Structural and catalytic analyses of the InsP kinase activities of higher plant ITPKs.高等植物 ITPK 的 InsP 激酶活性的结构和催化分析。
FASEB J. 2022 Jul;36(7):e22380. doi: 10.1096/fj.202200393R.
8
A structural exposé of noncanonical molecular reactivity within the protein tyrosine phosphatase WPD loop.蛋白质酪氨酸磷酸酶 WPD 环中非规范分子反应性的结构剖析。
Nat Commun. 2022 Apr 25;13(1):2231. doi: 10.1038/s41467-022-29673-y.
9
ITPK1 is an InsP/ADP phosphotransferase that controls phosphate signaling in Arabidopsis.ITPK1 是一种 InsP/ADP 磷酸转移酶,它控制着拟南芥中的磷酸信号转导。
Mol Plant. 2021 Nov 1;14(11):1864-1880. doi: 10.1016/j.molp.2021.07.011. Epub 2021 Jul 15.
10
New structural insights reveal an expanded reaction cycle for inositol pyrophosphate hydrolysis by human DIPP1.新的结构见解揭示了人类 DIPP1 水解肌醇焦磷酸的扩展反应循环。
FASEB J. 2021 Feb;35(2):e21275. doi: 10.1096/fj.202001489R.