期刊：
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY,2024年72(8):3884-3893 ISSN：0021-8561
通讯作者：
Lin, Hong-Yan;Wang, DW
作者机构：
[Ye, Bao-Qing; Yang, Guang-Fu; Cai, Zhuo-Mei; Chen, Li-Jun; Wang, Da-Wei; Dong, Jin; Huang, Guang-Yi; Lin, Hong-Yan; Lin, HY] Cent China Normal Univ, Natl Key Lab Green Pesticide, Wuhan 430079, Peoples R China.;[Ye, Bao-Qing; Yang, Guang-Fu; Cai, Zhuo-Mei; Chen, Li-Jun; Wang, Da-Wei; Dong, Jin; Huang, Guang-Yi; Lin, Hong-Yan; Lin, HY] Cent China Normal Univ, Coll Chem, Int Joint Res Ctr Intelligent Biosensor Technol &, Wuhan 430079, Peoples R China.
通讯机构：
[Wang, DW ; Lin, HY] C;Cent China Normal Univ, Natl Key Lab Green Pesticide, Wuhan 430079, Peoples R China.;Cent China Normal Univ, Coll Chem, Int Joint Res Ctr Intelligent Biosensor Technol &, Wuhan 430079, Peoples R China.
作者机构：
[Tang, Gege; Yang, Guangfu; Liu, Jiaxin; Chen, Huimin; Hao, Gefei] State Key Laboratory of Green Pesticide, College of Chemistry, Central China Normal University, Wuhan 430079, China;[Hao, Gefei] State Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for Research and Development of Fine chemicals of Guizhou University, Guiyang 550025, China
摘要：
Historically, there have been many outbreaks of viral diseases that have continued to claim millions of lives. Research on human-virus protein-protein interactions (PPIs) is vital to understanding the principles of human-virus relationships, providing an essential foundation for developing virus control strategies to combat diseases. The rapidly accumulating data on human-virus PPIs offer unprecedented opportunities for bioinformatics research around human-virus PPIs. However, available detailed analyses and summaries to help use these resources systematically and efficiently are lacking. Here, we comprehensively review the bioinformatic tools used in human-virus PPIs research, discuss and compare the function, performance, and limitations of these web resources. This study aims to provide researchers with a bioinformatic toolbox that will hopefully better facilitate the exploration of human-virus PPIs based on binding modes.
摘要：
Fosmidomycin (FOS) is a natural product inhibiting the DXR enzyme in the MEP pathway and has stimulated interest for finding more suitable FOS analogues. Herein, two series of FOS analogue hydroxamate-containing bisphosphonates as proherbicides were designed, with bisphosphonate replacing the phosphonic unit in FOS while retaining the hydroxamate (BPF series) or replacing it with retro-hydroxamate (BPRF series). The BPF series were synthesized through a three-step reaction sequence including Michael addition of vinylidenebisphosphonate, N-acylation, and deprotection, and the BPRF series were synthesized with a retro-Claisen condensation incorporated into the reaction sequence. Evaluation on model plants demonstrated several compounds having considerable herbicidal activities, and in particular, compound 8m exhibited multifold activity enhancement as compared to the control FOS. The proherbicide properties were comparatively validated. Furthermore, DXR enzyme assay, dimethylallyl pyrophosphate rescue, and molecular docking verified 8m to be a promising proherbicide candidate targeting the DXR enzyme. In addition, 8m also displayed good antimalarial activities.
摘要：
Drug discovery often begins with a new target. Protein-protein interactions (PPIs) are crucial to multitudinous cellular processes and offer a promising avenue for drug-target discovery. PPIs are characterized by multi-level complexity: at the protein level, interaction networks can be used to identify potential targets, whereas at the residue level, the details of the interactions of individual PPIs can be used to examine a target's druggability. Much great progress has been made in target discovery through multi-level PPI-related computational approaches, but these resources have not been fully discussed. Here, we systematically survey bioinformatics tools for identifying and assessing potential drug targets, examining their characteristics, limitations and applications. This work will aid the integration of the broader protein-to-network context with the analysis of detailed binding mechanisms to support the discovery of drug targets.
作者机构：
[Huang, Yurou; Xiao, Wang; Sun, Jiayue; Zeng, Xiaoyan; Liu, Sheng Hua; Lin, Zibo; Ma, Xiaoxie] State Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan, PR China;[Yin, Jun] State Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan, PR China. yinj@ccnu.edu.cn;[Yang, Guang-Fu] State Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan, PR China. gfyang@ccnu.edu.cn
摘要：
Azo switches are widely employed as essential components in light-responsive systems. Here, we develop an azo-fluorescent switch that is visible light-responsive and its light-responsive processes can be monitored using fluorescence imaging. Visible light irradiation promotes isomerization, accompanied by changes in fluorescence that enable the process to be monitored through fluorescence imaging. Furthermore, we document that the nanocavity size of liposome encapsulated nanoparticles containing azo changes in the isomerization process and show that this change enables construction of a light-responsive nanoplatform for optically controlled release of antimycotics. Also, natural light activation of nanoparticles of the switch loaded with an antimycotic agent causes death of Rhizoctonia solani. The results show that these nanoparticles can double the holding period in comparison to small molecule antimycotics. The strategy used to design the imaging-guided light-controlled nano-antimycotic release system can be applicable to protocols for controlled delivery of a wide variety of drugs.
作者机构：
[Huang, Yurou; Yin, Jun; Yang, Guang-Fu; Zeng, Xiaoyan; Liu, Sheng Hua; Yang, GF; Ma, Xiaoxie] Cent China Normal Univ, Coll Chem, Int Joint Res Ctr Intelligent Biosensor Technol &, State Key Lab Green Pesticide, Wuhan, Peoples R China.
通讯机构：
[Yin, J; Yang, GF ] C;Cent China Normal Univ, Coll Chem, Int Joint Res Ctr Intelligent Biosensor Technol &, State Key Lab Green Pesticide, Wuhan, Peoples R China.
摘要：
Salt stress is an adverse environmental condition that harms plant growth and development. The development of salt stress probes is critical for tracking the growth dynamics of plants, molecular breeding or screening of growth regulators. The sodium chloride (NaCl)-responsive fluorescent probe Aza-CyBz is designed based on the tenet that NaCl induces formation of ordered aggregates, and the sensitive fluorescence response can enable the visualization of plant salt stress in root tip tissues and live plants. Herein, we describe a detailed three-step route for synthesis of Aza-CyBz and applications to monitoring salt stress in Arabidopsis thaliana. The procedures for operating fluorescence imaging under various stresses are also listed to eliminate interference from the oxidative mechanism of salt stress. Compared with conventional invasive approaches such as inductively coupled plasma emission spectrometry and flame photometer, our protocol can real-time monitor salt stress experienced by plants, which demands simple pretreatment procedure and staining technique. Due to near infrared fluorescence, this method provides direct visual observation of salt stress at both tissue and live plant levels, which is superior to conventional noninvasive approaches. The preparation of probe Aza-CyBz takes similar to 2 d, and the imaging experiments for assessing salt stress experienced by plants, including the preparation of stressed plant samples takes similar to 9-11 d for root tip tissues and similar to 23 d for live plants. Notably, acquisition and analysis visual images of salt stress in plants can be completed within 2 h and they require only a basic knowledge of spectroscopy and chemistry.
期刊：
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY,2024年72(31):17649-17657 ISSN：0021-8561
通讯作者：
Zhu, Xiao-Lei;Yang, GF
作者机构：
[Yang, Jing-Fang; Chen, Wei; Zhu, Xiao-Lei; Zhu, XL; Li, Yi-Wen; Yang, Guang-Fu; Yang, GF; Li, Hong-Hao; Zhou, Li-Ming] Cent China Normal Univ, Int Joint Res Ctr Intelligent Biosensor Technol &, Minist Sci & Technol, State Key Lab Green Pesticide,Key Lab Pesticide &, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu; Yang, GF] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300071, Peoples R China.
通讯机构：
[Zhu, XL; Yang, GF ] C;Cent China Normal Univ, Int Joint Res Ctr Intelligent Biosensor Technol &, Minist Sci & Technol, State Key Lab Green Pesticide,Key Lab Pesticide &, Wuhan 430079, Peoples R China.;Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300071, Peoples R China.
关键词：
indole;oxathiapiprolin;substituent optimization;oxysterol-binding protein inhibitor;fungicide;interaction mechanism
摘要：
Oxathiapiprolin (OXA), which targets the oxysterol-binding protein (OSBP), is an outstanding piperidinyl thiazole isoxazoline (PTI) fungicide that can be used to control oomycetes diseases. In this study, starting from the structure of OXA, a series of novel OSBP inhibitors were designed and synthesized by introducing an indole moiety to replace the pyrazole in OXA. Finally, compound b24 was found to exhibit the highest control effect (82%) against cucumber downy mildew (CDM) in the greenhouse at a very low dosage of 0.069 mg/L, which was comparable to that of OXA (88%). Furthermore, it showed better activity against potato late blight (PLB) than other derivatives of indole. The computational results showed that the R-conformation of b24 should be the dominant conformation binding to PcOSBP. The results of the present work indicate that the 3-fluorine-indole ring is a favorable fragment to increasing the electronic energy when binding with PcOSBP. Furthermore, compound b24 could be used as a lead compound for the discovery of new OSBP inhibitors.
期刊：
Drug Discovery Today,2023年:103546 ISSN：1359-6446
通讯作者：
Li, Qing X;Yang, Guang-Fu
作者机构：
[Yang, Jing-Fang; Yang, Guang-Fu; Wang, Meng-Yao; Wang, Di; Wang, Fan; Hao, Ge-Fei] Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China;[Yang, Jing-Fang; Yang, Guang-Fu; Wang, Meng-Yao; Wang, Di; Wang, Fan; Hao, Ge-Fei] International Joint Research Center for Intelligent Biosensor Technology and Health, Central China Normal University, Wuhan, 430079, PR China;[Yang, Jing-Fang] State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, PR China;[Zhou, Zhong-Shi] State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, PR China;[Hao, Ge-Fei] State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Research and Development Center for Fine Chemicals, Guizhou University, Guiyang 550025, PR China
通讯机构：
[Li, Qing X] D;[Yang, Guang-Fu] C;Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, Honolulu, HI 96822, USA. Electronic address:;Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, PR China. Electronic address:
摘要：
As major forces for modulating protein folding and molecular recognition, cation-π interactions are extensively identified in protein structures. They are even more competitive than hydrogen bonds in molecular recognition and, thus, are vital in numerous biological processes. In this review, we introduce the methods for the identification and quantification of cation-π interactions, provide insights into the characteristics of cation-π interactions in the natural state, and reveal their biological function together with our developed database (Cation-π Interaction in Protein Data Bank; CIPDB; http://chemyang.ccnu.edu.cn/ccb/database/CIPDB). This review lays the foundation for the in-depth study of cation-π interactions and will guide the use of molecular design for drug discovery. Teaser: We provide an overview of the cation-π interaction from its emergence to measurement and collection, along with a data set developed by us, which guides further research in biology and drug design.
通讯机构：
[Guang-Fu Yang; Jun Guo] K;Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensing Technology and Health, Hubei International Scientific and Technological Cooperation Base of Pesticide and Green Synthesis, College of Chemistry, Central China Normal University, Wuhan 430079, China
摘要：
Developing a novel and potent adjuvant with great biocompatibility for immune response augmentation is of great significance to enhance vaccine efficacy. In this work, we prepared a long-term stable, pH-sensitive, and biodegradable Mn(3)(PO(4))(2)·3H(2)O nanoparticle (nano-MnP) by simply mixing MnCl(2)/NaH(2)PO(4)/Na(2)HPO(4) solution for the first time and employed it as an immune stimulant in the bivalent COVID-19 protein vaccine comprised of wild-type S1 (S1-WT) and Omicron S1 (S1-Omicron) proteins as antigens to elicit a broad-spectrum immunity. The biological experiments indicated that the nano-MnP could effectively activate antigen-presenting cells through the cGAS-STING pathway. Compared with the conventional Alum-adjuvanted group, the nano-MnP-adjuvanted bivalent vaccine elicited approximately 7- and 8-fold increases in IgG antibody titers and antigen-specific IFN-γ secreting T cells, respectively. Importantly, antisera of the nano-MnP-adjuvanted group could effectively cross-neutralize the SARS-CoV-2 and its five variants of concern (VOCs) including Alpha, Beta, Gamma, Delta, and Omicron, demonstrating that this bivalent vaccine based on S1-WT and S1-Omicron proteins is an effective vaccine design strategy to induce broad-spectrum immune responses. Collectively, this nano-MnP material may provide a novel and efficient adjuvant platform for various prophylactic and therapeutic vaccines and provide insights for the development of the next-generation manganese adjuvant.
作者机构：
[Yin, Jun; Yang, Guang-Fu; Zeng, Xiaoyan; Yang, GF; Li, Biao; Hua Liu, Sheng; Dong, Jin; Ma, Xiaoxie] Cent China Normal Univ, Coll Chem, Int Joint Res Ctr Intelligent Biosensor Technol &, Natl Key Lab Green Pesticide, Wuhan 430079, Peoples R China.
通讯机构：
[Yin, J; Yang, GF ] C;Cent China Normal Univ, Coll Chem, Int Joint Res Ctr Intelligent Biosensor Technol &, Natl Key Lab Green Pesticide, Wuhan 430079, Peoples R China.
摘要：
4-Hydroxyphenylpyruvate dioxygenase (HPPD) plays a crucial role in the synthesis of nutrients needed to maintain optimal plant growth. Its level is closely linked to the extent of abiotic stress experienced by plants. Moreover, it is also the target of commercial herbicides. Therefore, labeling of HPPD in plants not only enables visualization of its tissue distribution and cellular uptake, it also facilitates assessment of abiotic stress of plants and provides information needed for the development of effective environmentally friendly herbicides. In this study, we created a method for fluorescence labeling of HPPD that avoids interference with the normal growth of plants. In this strategy, a perylene-linked dibenzyl-cyclooctyne undergoes strain-promoted azide-alkyne cycloaddition with an azide-containing HPPD ligand. The activation-based labeling process results in a significant emission enhancement caused by the change in the fluorescent forms from an excimer to a monomer. Notably, this activated bioorthogonal strategy is applicable to visualizing HPPD in Arabidopsis thaliana, and assessing its response to multiple abiotic stresses. Also, it can be employed to monitor in vivo levels and locations of HPPD in crops. Consequently, the labeling strategy will be a significant tool in investigations of HPPD-related abiotic stress mechanisms, discovering novel herbicides, and uncovering unknown biological functions.
期刊：
Trends in Biochemical Sciences,2023年48(6):539-552 ISSN：0968-0004
通讯作者：
Hao, Ge-Fei;Yang, GF;Hao, GF
作者机构：
[Yang, Guang-Fu; Wang, Zhi-Zheng; Yang, GF; Shi, Xing-Xing; Huang, Guang-Yi; Hao, Ge-Fei] Cent China Normal Univ, Natl Key Lab Green Pesticide, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.;[Hao, Ge-Fei] Guizhou Univ, Ctr R&D Fine Chem, Natl Key Lab Green Pesticide, Key Lab Green Pesticide & Agr BioEngn,Minist Educ, Guiyang 550025, Peoples R China.
通讯机构：
[Hao, GF ] G;[Yang, GF ; Hao, GF] C;Cent China Normal Univ, Natl Key Lab Green Pesticide, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.;Guizhou Univ, Ctr R&D Fine Chem, Natl Key Lab Green Pesticide, Key Lab Green Pesticide & Agr BioEngn,Minist Educ, Guiyang 550025, Peoples R China.
关键词：
PPI modulator;fragment evolution;fragment screening;hot spot;structure-based drug design
摘要：
Protein-protein interactions (PPIs) have important roles in various cellular processes, but are commonly described as 'undruggable' therapeutic targets due to their large, flat, featureless interfaces. Fragment-based drug discovery (FBDD) has achieved great success in modulating PPIs, with more than ten compounds in clinical trials. Here, we highlight the progress of FBDD in modulating PPIs for therapeutic development. Targeting hot spots that have essential roles in both fragment binding and PPIs provides a shortcut for the development of PPI modulators via FBDD. We highlight successful cases of cracking the 'undruggable' problems of PPIs using fragment-based approaches. We also introduce new technologies and future trends. Thus, we hope that this review will provide useful guidance for drug discovery targeting PPIs.
摘要：
4-Hydroxyphenylpyruvate dioxygenase (HPPD) plays a key role in tyrosine metabolism and has been identified as a promising target for herbicide and drug discovery. The structures of HPPD complexed with different types of inhibitors have been determined previously. We summarize the structures of HPPD complexed with structurally diverse molecules, including inhibitors, natural products, substrates, and catalytic intermediates; from these structures, the detailed inhibitory mechanisms of different inhibitors were analyzed and compared, and the key structural factors determining the slow-binding behavior of inhibitors were identified. Further, we propose four subpockets that accommodate different inhibitor substructures. We believe that these analyses will facilitate in-depth understanding of the enzymatic reaction mechanism and enable the design of new inhibitors with higher potency and selectivity.
期刊：
Drug Discovery Today,2023年28(5):103546 ISSN：1359-6446
通讯作者：
Ge-Fei Hao<&wdkj&>Qing X. Li<&wdkj&>Guang-Fu Yang
作者机构：
[Yang, Jing-Fang; Yang, Guang-Fu; Wang, Meng-Yao; Wang, Di; Wang, Fan; Hao, Ge-Fei] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.;[Yang, Jing-Fang; Yang, Guang-Fu; Wang, Meng-Yao; Wang, Di; Wang, Fan; Hao, Ge-Fei] Cent China Normal Univ, Int Joint Res Ctr Intelligent Biosensor Technol &, Wuhan 430079, Peoples R China.;[Yang, Jing-Fang; Zhou, Zhong-Shi] Chinese Acad Agr Sci, Inst Plant Protect, State Key Lab Biol Plant Dis & Insect Pests, Beijing 100193, Peoples R China.;[Hao, Ge-Fei] Guizhou Univ, Res & Dev Ctr Fine Chem, State Key Lab Breeding Base Green Pesticide & Agr, Key Lab Green Pesticide & Agr Bioengn,Minist Educ, Guiyang 550025, Peoples R China.;[Li, Qing X.] Univ Hawaii Manoa, Dept Mol Biosci & Bioengn, Honolulu, HI 96822 USA.
通讯机构：
[Ge-Fei Hao; Guang-Fu Yang] K;[Qing X. Li] D;Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China<&wdkj&>International Joint Research Center for Intelligent Biosensor Technology and Health, Central China Normal University, Wuhan 430079, PR China<&wdkj&>State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Research and Development Center for Fine Chemicals, Guizhou University, Guiyang 550025, PR China<&wdkj&>Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, Honolulu, HI 96822, USA<&wdkj&>Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China<&wdkj&>International Joint Research Center for Intelligent Biosensor Technology and Health, Central China Normal University, Wuhan 430079, PR China<&wdkj&>Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, PR China
通讯作者：
Prof. Jun Yin<&wdkj&>Prof. Guang-Fu Yang<&wdkj&>Prof. Jun Yin Prof. Jun Yin Prof. Jun Yin<&wdkj&>Prof. Guang-Fu Yang Prof. Guang-Fu Yang Prof. Guang-Fu Yang
作者机构：
[Xiaoxie Ma; Yurou Huang; Weijie Chen; Jia Liu; Prof. Sheng Hua Liu; Prof. Jun Yin; Prof. Guang-Fu Yang; Xiaoxie Ma Xiaoxie Ma Xiaoxie Ma; Yurou Huang Yurou Huang Yurou Huang; Weijie Chen Weijie Chen Weijie Chen; Jia Liu Jia Liu Jia Liu; Prof. Sheng Hua Liu Prof. Sheng Hua Liu Prof. Sheng Hua Liu; Prof. Jun Yin Prof. Jun Yin Prof. Jun Yin; Prof. Guang-Fu Yang Prof. Guang-Fu Yang Prof. Guang-Fu Yang] Key Laboratory of Pesticide and Chemical Biology (Ministry of Education), Hubei International Scientific and Technological Cooperation Base of Pesticide and Green Synthesis, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan, 430079 P. R. China
通讯机构：
[Prof. Jun Yin; Prof. Guang-Fu Yang; Prof. Jun Yin Prof. Jun Yin Prof. Jun Yin; Prof. Guang-Fu Yang Prof. Guang-Fu Yang Prof. Guang-Fu Yang] K;Key Laboratory of Pesticide and Chemical Biology (Ministry of Education), Hubei International Scientific and Technological Cooperation Base of Pesticide and Green Synthesis, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan, 430079 P. R. China
摘要：
<jats:title>Abstract</jats:title><jats:p>The cationic nature of heptamethine cyanines gives them the capacity to form aggregates with salts by electrostatic interactions. In this work, NaCl promoted J‐aggregate formation of aza‐coating heptamethine cyanines is explored. NaCl can induce the<jats:italic>N</jats:italic>‐benzyloxycarbonyl<jats:bold>Cy‐CO<jats:sub>2</jats:sub>Bz</jats:bold>to assemble into a J‐aggregate having an absorption at 890 nm. Its excellent fluorescence response to NaCl implies that it has great potential for use as a probe for tracing salt stress in plants. Moreover, NaCl also promotes formation of J‐aggregates from the N‐ethyloxycarbonyl<jats:bold>Cy‐CO<jats:sub>2</jats:sub>Et</jats:bold>. The aggregate shows an intense absorption at 910 nm compared to the monomer which absorbs at 766 nm. Its J‐aggregated form can serve as a photothermal agent. And the photothermal conversion efficiency is increased from 29.37 % to 57.59 %. This effort leads to the development of two applications of new cyanine J‐aggregates including one for tracing salt stress of plants and the other for promoting photothermal therapy of tumors.</jats:p>
作者机构：
[Xin Li; Xinyun Zhao; Xi Chen; Linhui Li] College of Chemistry and Material Science,South-Central Minzu University,Wuhan 430074,China;School of Pharmacy,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Key Laboratory of Pesticide&Chemical Biology of Ministry of Education,College of Chemistry,Central China Normal University,Wuhan 430079,China;Department of Pharmaceutical Sciences,College of Pharmacy,University of Kentucky,Lexington,KY 40536,United States;[Guangfu Yang; Hongyan Lin] 华中师范大学
摘要：
The dioxygen activation catalyzed by 4-hydorxylphenyl pyruvate dioxygenase(HPPD)were reinvesti-gated by using hybrid quantum mechanics/molecular mechanics(QM/MM)approaches at the B3LYP/6-311++G(d,p):AMBER level.These studies showed that this reaction consisted of two steps including the dioxygen addition/decarboxylation and hetero O-O bond cleavage,where the first step was found to be rate-determining.The former step initially runs on a septet potential energy surface(PES),then switches to a quintet PES after crossing a septet/quintet minimum energy crossing point(MECP)5-7M2,whereas the rest step runs on the quintet PES.The reliability of our theoretical predictions is supported by the excellent agreement of the calculated free-energy barrier value of 16.9kcal/mol with available experi-mental value of 16-17 kcal/mol.The present study challenges the widely accepted view which holds that the O2 activation catalyzed by α-keto glutamate(α-KG)dioxygenase mainly runs on the quintet PES and provides new insight into the catalytic mechanism of α-KG dioxygenase and/or other related Fe(Ⅱ)-dependent oxygenase.
期刊：
Trends in Biotechnology,2023年41(2):140-143 ISSN：0167-7799
通讯作者：
Ge-Fei Hao<&wdkj&>Guang-Fu Yang
作者机构：
[Long-Can Mei; Ge-Fei Hao] Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China;[Ge-Fei Hao] State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Research and Development Center for Fine Chemicals, Guizhou University, Guiyang 550000, China. Electronic address: gefei_hao@foxmail.com;[Guang-Fu Yang] Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China. Electronic address: gfyang@mail.ccnu.edu.cn
通讯机构：
[Ge-Fei Hao; Guang-Fu Yang] K;Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China<&wdkj&>State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Research and Development Center for Fine Chemicals, Guizhou University, Guiyang 550000, China<&wdkj&>Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China
期刊：
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY,2023年71(1):52-64 ISSN：0021-8561
通讯作者：
Ge-Fei Hao<&wdkj&>Guang-Fu Yang
作者机构：
[Sun, Hao-Han; Yang, Guang-Fu; Wang, Zhi-Zheng; Hao, Ge-Fei] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.;[Gao, Yang-Yang; Hao, Ge-Fei] Guizhou Univ, Res & Dev Ctr Fine Chem, State Key Lab Breeding Base Green Pesticide & Agr, Key Lab Green Pesticide & Agr Bioengn,Minist Educ, Guiyang 550025, Peoples R China.
通讯机构：
[Ge-Fei Hao; Guang-Fu Yang] K;Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, People’s Republic of China<&wdkj&>State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Research and Development Center for Fine Chemicals, Guizhou University, Guiyang 550025, People’s Republic of China<&wdkj&>Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, People’s Republic of China
关键词：
protein kinases;targetability;antifungals;stress tolerance;plant immunity;agrochemicals discovery
摘要：
Using agrochemicals against pest insects, fungi, and weeds plays a major part in maintaining and improving crop yields, which helps to solve the issue of food security. Due to the limited targets and resistance of agrochemicals, protein kinases are regarded as attractive potential targets to develop new agrochemicals. Recently, a lot of investigations have shown the extension of agrochemicals by targeting protein kinases, implying an increasing concern for this kind of method. However, few people have summarized and discussed the targetability of protein kinases contributing to the development of agrochemicals. In this work, we introduce the research on protein kinases as potential targets used in crop protection and discuss the prospects of protein kinases in the field of agrochemical development. This study may not only provide guidance for the contribution of protein kinases to the development of agrochemicals but also help nonprofessionals such as students learn and understand the role of protein kinases quickly.
