Binding asymmetry and conformational studies of the AtGSDA dimer
Guanosine deaminase (GSDA) is an important deaminase that converts guanosine to xanthosine, a key intermediate in nitrogen recycling in plants. We previously solved complex structures of Arabidopsis thaliana GSDA bound by various ligands and examined its catalytic mechanism. Here, we report cocrysta...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037023004208 |
| _version_ | 1797384043666341888 |
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| author | Qian Jia Hui Zeng Mingwei Li Jing Tang Nan Xiao Shangfang Gao Huanxi Li Jinbing Zhang Zhiyong Zhang Wei Xie |
| author_facet | Qian Jia Hui Zeng Mingwei Li Jing Tang Nan Xiao Shangfang Gao Huanxi Li Jinbing Zhang Zhiyong Zhang Wei Xie |
| author_sort | Qian Jia |
| collection | DOAJ |
| description | Guanosine deaminase (GSDA) is an important deaminase that converts guanosine to xanthosine, a key intermediate in nitrogen recycling in plants. We previously solved complex structures of Arabidopsis thaliana GSDA bound by various ligands and examined its catalytic mechanism. Here, we report cocrystal structures of AtGSDA bound by inactive guanosine derivatives, which bind relatively weakly to the enzyme and mostly have poor binding geometries. The two protomers display unequal binding performances, and molecular dynamics simulation identified diverse conformations during the enzyme-ligand interactions. Moreover, intersubunit, tripartite salt bridges show conformational differences between the two protomers, possibly acting as “gating” systems for substrate binding and product release. Our structural and biochemical studies provide a comprehensive understanding of the enzymatic behavior of this intriguing enzyme. |
| first_indexed | 2024-03-08T21:29:46Z |
| format | Article |
| id | doaj.art-02684f9ddc7346f3a8ec60e35cef295b |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-03-08T21:29:46Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-02684f9ddc7346f3a8ec60e35cef295b2023-12-21T07:32:29ZengElsevierComputational and Structural Biotechnology Journal2001-03702023-01-012155155522Binding asymmetry and conformational studies of the AtGSDA dimerQian Jia0Hui Zeng1Mingwei Li2Jing Tang3Nan Xiao4Shangfang Gao5Huanxi Li6Jinbing Zhang7Zhiyong Zhang8Wei Xie9MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510006, People's Republic of ChinaMOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510006, People's Republic of ChinaDivision of Life Sciences and Medicine, and Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China, Hefei, Anhui 230026, PR ChinaMOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510006, People's Republic of ChinaMOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510006, People's Republic of ChinaMOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510006, People's Republic of ChinaMOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510006, People's Republic of ChinaMOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510006, People's Republic of ChinaMOE Key Laboratory for Membraneless Organelles & Cellular Dynamics, Department of Physics, University of Science and Technology of China, Hefei, Anhui 230026, PR China; Corresponding authors.MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510006, People's Republic of China; Corresponding authors.Guanosine deaminase (GSDA) is an important deaminase that converts guanosine to xanthosine, a key intermediate in nitrogen recycling in plants. We previously solved complex structures of Arabidopsis thaliana GSDA bound by various ligands and examined its catalytic mechanism. Here, we report cocrystal structures of AtGSDA bound by inactive guanosine derivatives, which bind relatively weakly to the enzyme and mostly have poor binding geometries. The two protomers display unequal binding performances, and molecular dynamics simulation identified diverse conformations during the enzyme-ligand interactions. Moreover, intersubunit, tripartite salt bridges show conformational differences between the two protomers, possibly acting as “gating” systems for substrate binding and product release. Our structural and biochemical studies provide a comprehensive understanding of the enzymatic behavior of this intriguing enzyme.http://www.sciencedirect.com/science/article/pii/S2001037023004208Binding asymmetryGuanosine deaminaseMolecular dynamics simulationPurine metabolismUnequal conformation |
| spellingShingle | Qian Jia Hui Zeng Mingwei Li Jing Tang Nan Xiao Shangfang Gao Huanxi Li Jinbing Zhang Zhiyong Zhang Wei Xie Binding asymmetry and conformational studies of the AtGSDA dimer Computational and Structural Biotechnology Journal Binding asymmetry Guanosine deaminase Molecular dynamics simulation Purine metabolism Unequal conformation |
| title | Binding asymmetry and conformational studies of the AtGSDA dimer |
| title_full | Binding asymmetry and conformational studies of the AtGSDA dimer |
| title_fullStr | Binding asymmetry and conformational studies of the AtGSDA dimer |
| title_full_unstemmed | Binding asymmetry and conformational studies of the AtGSDA dimer |
| title_short | Binding asymmetry and conformational studies of the AtGSDA dimer |
| title_sort | binding asymmetry and conformational studies of the atgsda dimer |
| topic | Binding asymmetry Guanosine deaminase Molecular dynamics simulation Purine metabolism Unequal conformation |
| url | http://www.sciencedirect.com/science/article/pii/S2001037023004208 |
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