https://scholars.lib.ntu.edu.tw/handle/123456789/572715
標題: | Elucidating the tunability of binding behavior for the MERS-CoV macro domain with NAD metabolites | 作者: | Lin M.-H Cho C.-C Chiu Y.-C Chien C.-Y Huang Y.-P Chang C.-F CHUN-HUA HSU |
關鍵字: | adenosine diphosphate ribose; ligand; nicotinamide adenine dinucleotide; poly(adenosine diphosphate ribose); protein binding; viral protein; binding site; biophysics; chemistry; crystallization; human; metabolism; Middle East respiratory syndrome coronavirus; molecular model; nuclear magnetic resonance; protein domain; protein stability; thermodynamics; X ray crystallography; Adenosine Diphosphate Ribose; Binding Sites; Biophysical Phenomena; Crystallization; Crystallography, X-Ray; Humans; Ligands; Middle East Respiratory Syndrome Coronavirus; Models, Molecular; NAD; Nuclear Magnetic Resonance, Biomolecular; Poly Adenosine Diphosphate Ribose; Protein Binding; Protein Domains; Protein Stability; Thermodynamics; Viral Proteins | 公開日期: | 2021 | 卷: | 4 | 期: | 1 | 來源出版物: | Communications Biology | 摘要: | The macro domain is an ADP-ribose (ADPR) binding module, which is considered to act as a sensor to recognize nicotinamide adenine dinucleotide (NAD) metabolites, including poly ADPR (PAR) and other small molecules. The recognition of macro domains with various ligands is important for a variety of biological functions involved in NAD metabolism, including DNA repair, chromatin remodeling, maintenance of genomic stability, and response to viral infection. Nevertheless, how the macro domain binds to moieties with such structural obstacles using a simple cleft remains a puzzle. We systematically investigated the Middle East respiratory syndrome-coronavirus (MERS-CoV) macro domain for its ligand selectivity and binding properties by structural and biophysical approaches. Of interest, NAD, which is considered not to interact with macro domains, was co-crystallized with the MERS-CoV macro domain. Further studies at physiological temperature revealed that NAD has similar binding ability with ADPR because of the accommodation of the thermal-tunable binding pocket. This study provides the biochemical and structural bases of the detailed ligand-binding mode of the MERS-CoV macro domain. In addition, our observation of enhanced binding affinity of the MERS-CoV macro domain to NAD at physiological temperature highlights the need for further study to reveal the biological functions. ? 2021, The Author(s). |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85099861875&doi=10.1038%2fs42003-020-01633-6&partnerID=40&md5=cda67431782246d858f4ca4934ef5b7c https://scholars.lib.ntu.edu.tw/handle/123456789/572715 |
ISSN: | 23993642 | DOI: | 10.1038/s42003-020-01633-6 |
顯示於: | 農業化學系 |
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