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| Structure-Dependent Modulation of Substrate Binding and Biodegradation Activity of Pirin Proteins toward Plant Flavonols | |
| Guo, Bin1; Zhang, Yichen2; Hicks, Gregory2; Huang, Xingrong1; Li, Rongfeng3; Roy, Natalie2; Jia, Zongchao2 | |
| 2019-12-01 | |
| 发表期刊 | ACS CHEMICAL BIOLOGY
 |
| ISSN | 1554-8929 |
| 卷号 | 14期号:12页码:2629-2640 |
| 摘要 | Pirin is a nonheme metalloprotein that occurs widely in human tissues and is highly conserved across all taxa. Pirin proteins typically function as nuclear transcription regulators, but two Pirin orthologs, YhhW (from Escherichia coli) and hPirin (from humans) were revealed to possess enzymatic activity of degrading quercetin. The exact role of Pirin homologues and their catalytic specificity remain poorly understood. In this work, by screening against a panel of plant flavonoids, we found that both Pirins catalyze the oxidative degradation of a wide spectrum of flavonol analogues and release carbon monoxide (CO) in the process. This shows that Pirin acts on a broad range of substrates and could represent a novel dietary source of CO in vivo. Although the kinetic profiles differ substantially between two Pirins, the identified substrate structures all share a 2,3-double bond and 3-hydroxyl and 4-oxo groups on their "flavonol backbone," which contribute to the specific enzyme substrate interaction. While hPirin is iron-dependent, YhhW is identified as a novel nickel containing dioxygenase member of the bicupin family. Besides the expanded Pirin activity, we present the crystal structures of the native Ni-YhhW and tag-free Fe-hPirin, revealing the distinctive differences occurring at the metal-binding site. In addition, YhhW features a flexible Omega-loop near the catalytic cavity, which may help stabilize the reaction intermediates via a Ni-flavonol complex. The structure-dependent modulation of substrate binding to the catalytic cavity adds to understanding the differential dispositions of natural flavonols by human and bacterial Pirins. |
| DOI | 10.1021/acschembio.9b00575 |
| 收录类别 | SCI |
| 语种 | 英语 |
| 资助项目 | Natural Sciences and Engineering Research Council of Canada[RGPIN-2018-04427] ; China Scholarship Council[201606725024] ; Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Education Ministry of China), Hunan Normal University[KLCBTCMR18-08] ; National Natural Science Foundation of China[81274178] ; National Natural Science Foundation of China[81274178] ; Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Education Ministry of China), Hunan Normal University[KLCBTCMR18-08] ; China Scholarship Council[201606725024] ; Natural Sciences and Engineering Research Council of Canada[RGPIN-2018-04427] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| WOS类目 | Biochemistry & Molecular Biology |
| WOS记录号 | WOS:000504806100016 |
| 出版者 | AMER CHEMICAL SOC |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 版本 | 出版稿 |
| 条目标识符 | http://ir.qdio.ac.cn/handle/337002/164125 |
| 专题 | 实验海洋生物学重点实验室 |
| 通讯作者 | Jia, Zongchao |
| 作者单位 | 1.Hunan Normal Univ, Educ Minist China, Key Lab Chem Biol & Tradit Chinese Med Res, Key Lab Phytochem R&D Hunan Prov, Changsha 410081, Hunan, Peoples R China 2.Queens Univ, Dept Biomed & Mol Sci, Kingston, ON K7L 3N6, Canada 3.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao 266071, Shandong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Guo, Bin,Zhang, Yichen,Hicks, Gregory,et al. Structure-Dependent Modulation of Substrate Binding and Biodegradation Activity of Pirin Proteins toward Plant Flavonols[J]. ACS CHEMICAL BIOLOGY,2019,14(12):2629-2640. |
| APA | Guo, Bin.,Zhang, Yichen.,Hicks, Gregory.,Huang, Xingrong.,Li, Rongfeng.,...&Jia, Zongchao.(2019).Structure-Dependent Modulation of Substrate Binding and Biodegradation Activity of Pirin Proteins toward Plant Flavonols.ACS CHEMICAL BIOLOGY,14(12),2629-2640. |
| MLA | Guo, Bin,et al."Structure-Dependent Modulation of Substrate Binding and Biodegradation Activity of Pirin Proteins toward Plant Flavonols".ACS CHEMICAL BIOLOGY 14.12(2019):2629-2640. |
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| Structure-Dependent （6597KB） | 期刊论文 | 作者接受稿 | 限制开放 | CC BY-NC-SA | 浏览 | |
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