Allosteric Activation of Transglutaminase 2 via Inducing an “Open” Conformation for Osteoblast Differentiation
Abstract: Osteoblasts play an important role in the regulation of bone homeostasis throughout life. Thus, the damage of osteoblasts can lead to serious skeletal diseases, highlighting the urgent need for novel pharmacological targets. This study introduces chemical genetics strategy by using small molecule forskolin (FSK) as a probe to explore the druggable targets for osteoporosis. Here, this work reveals that transglutaminase 2 (TGM2) served as a major cellular target of FSK to obviously induce osteoblast differentiation. Then, this work identifies a previously undisclosed allosteric site in the catalytic core of TGM2. In particular, FSK formed multiple hydrogen bonds in a saddle‐like domain to induce an “open” conformation of the β‐sandwich domain in TGM2, thereby promoting the substrate protein crosslinks by incorporating polyamine. Furthermore, this work finds that TGM2 interacted with several mitochondrial homeostasis‐associated proteins to improve mitochondrial dynamics and ATP production for osteoblast differentiation. Finally, this work observes that FSK effectively ameliorated osteoporosis in the ovariectomy mice model. Taken together, these findings show a previously undescribed pharmacological allosteric site on TGM2 for osteoporosis treatment, and also provide an available chemical tool for interrogating TGM2 biology and developing bone anabolic agent.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Allosteric Activation of Transglutaminase 2 via Inducing an “Open” Conformation for Osteoblast Differentiation ; day:23 ; month:04 ; year:2023 ; extent:12
Advanced science ; (23.04.2023) (gesamt 12)
- Creator
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Yang, Zhuo
Zhang, Xiao‐Wen
Zhuo, Fang‐Fang
Liu, Ting‐Ting
Luo, Qian‐Wei
Zheng, Yong‐Zhe
Li, Ling
Yang, Heng
Zhang, Yi‐Chi
Wang, Yan‐Hang
Liu, Dan
Tu, Peng‐Fei
Zeng, Ke‐Wu
- DOI
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10.1002/advs.202206533
- URN
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urn:nbn:de:101:1-2023042515090933221779
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 10:45 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Yang, Zhuo
- Zhang, Xiao‐Wen
- Zhuo, Fang‐Fang
- Liu, Ting‐Ting
- Luo, Qian‐Wei
- Zheng, Yong‐Zhe
- Li, Ling
- Yang, Heng
- Zhang, Yi‐Chi
- Wang, Yan‐Hang
- Liu, Dan
- Tu, Peng‐Fei
- Zeng, Ke‐Wu
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Role of inducible Nitric Oxide Synthase and Histone Deacetylase in Human Lung Epithelial Cell Model of Inflammation and Steroid Insensitivity
Effects of procyanidin on cardiomyocyte apoptosis after myocardial ischemia reperfusion in rats
The New Cooperative Medical Scheme (NCMS) and its implications for access to health care and medical expenditure: Evidence from rural China
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Simulated lateral tunneling for treating a huge submucosal tumor at the cervical esophagus
Two results on the value distribution of meromorphic functions
A comparison of methods for corrosion inhibitor assessment: Mild steel protected by disubstituted aromatics
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NaI/PPh3-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles
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Concentration-dependent corrosion inhibition with electrochemical energy conversion systems by a disubstituted aromatic: A comparison of methods
Allosteric Activation of Transglutaminase 2 via Inducing an “Open” Conformation for Osteoblast Differentiation (Adv. Sci. 18/2023)
Role of inducible Nitric Oxide Synthase and Histone Deacetylase in Human Lung Epithelial Cell Model of Inflammation and Steroid Insensitivity
Effects of procyanidin on cardiomyocyte apoptosis after myocardial ischemia reperfusion in rats
The New Cooperative Medical Scheme (NCMS) and its implications for access to health care and medical expenditure: Evidence from rural China
Endoscopic submucosal dissection for laterally spreading tumor inside gallbladder: A novel organ preserving option
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