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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
Source PublicationACS CHEMICAL BIOLOGY
ISSN1554-8929
Volume14Issue:12Pages:2629-2640
AbstractPirin 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.
DOI10.1021/acschembio.9b00575
Indexed BySCI
Language英语
Funding ProjectNational 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 Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000504806100016
PublisherAMER CHEMICAL SOC
Citation statistics
Document Type期刊论文
Version出版稿
Identifierhttp://ir.qdio.ac.cn/handle/337002/164125
Collection实验海洋生物学重点实验室
Corresponding AuthorJia, Zongchao
Affiliation1.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
Recommended Citation
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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