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| 1 | Crystal structure of SARS-CoV-2 main protease in complex with protease inhibitor PF-07321332显示文摘Dear Editor,Since December 2019,the pandemic of coronavirus disease 2019(COVID-19)has taken a heavy toll on global health,creating an urgent need to develop effective strategies for prevention and treatment.The etiological agent,known as severe acute respiratory syndrome coronavirus 2(SARSCoV-2),has infected nearly 229.2 million people worldwide with more than 4.7 million deaths as of September 15,2021.Older age and preexisting health conditions are associated with worse clinical prognosis including higher mortality rates(Zhou et al.,2020).The global race to combat this pandemic has led to rapid deployment of numerous effective vaccines against SARS-CoV-2(Tregoning et al.,2021).However,the emergence of viral variants,including the Delta variant(B.1.617.2),compromised vaccine effectiveness with resurgence of SARS-CoV-2 infection among highly vaccinated population(Keehner et al.,2021).Therefore,development of therapeutics against the more conserved viral targets would be essential to contain the spread of COVID-19 and reduce mortality. | Yao Zhao Chao Fang Qi Zhang Ruxue Zhang Xiangbo Zhao Yinkai Duan Haofeng Wang Yan Zhu Lu Feng Jinyi Zhao Maolin Shao Xiuna Yang Leike Zhang Chao Peng Kailin Yang Dawei Ma Zihe Rao Haitao Yang | 2022 | Protein & Cell2022，13，9： | 6 |
| 2 | High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors显示文摘A new coronavirus(SARS-CoV-2)has been identified as the etiologic agent for the COVID-19 outbreak.Currently,effective treatment options remain very limited for this disease;therefore,there is an urgent need to identify new anti-COVID-19 agents.In this study,we screened over 6,000 compounds that included approved drugs,drug candidates in clinical trials,and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease(PLpro).Together with main protease(Mpro),PLpro is responsible for processing the viral replicase polyprotein into functional units.There-fore,it is an attractive target for antiviral drug develop-ment.Here we discovered four compounds,YM155,cryptotanshinone,tanshinone I and GRL0617 that inhibit SARS-CoV-2 PLpro with IC50 values ranging from 1.39 to 5.63 pmol/L.These compounds also exhibit strong antiviral activities in cell-based assays.YM155,an anti-cancer drug candidate in clinical trials,has the most potent antiviral activity with an EC50 value of 170 nmol/L.In addition,we have determined the crystal structures of this enzyme and its complex with YM155,revealing a unique binding mode.YM155 simultaneously targets three'hot'spots on PLpro,including the substrate-binding pocket,the interferon stimulating gene product 15(ISG15)binding site and zinc finger motif.Our results demonstrate the efficacy of this screening and repur-posing strategy,which has led to the discovery of new drug leads with clinical potential for COVID-19 treatments. | Yao Zhao Xiaoyu Du Yinkai Duan Xiaoyan Pan Yifang Sun Tian You Lin Han Zhenming Jin Weijuan Shang Jing Yu Hangtian Guo Qianying Liu Yan Wu Chao Peng Jun Wang Chenghao Zhu Xiuna Yang Kailin Yang Ying Lei Luke W.Guddat Wenqing Xu Gengfu Xiao Lei Sun Leike Zhang Zihe Rao Haitao Yang | 2021 | Protein & Cell2021，12，11： | 4 |
| 3 | Structural insights into substrate recognition by the type Ⅶ secretion system显示文摘Type VII secretion systems(T7SSs)are found in many disease related bacteria including Mycobacterium tuberculosis(Mtb).ESX-1[early secreted antigen 6 kilodaltons(ESAT-6)system 1]is one of the five subtypes(ESX-1?5)of T7SSs in Mfb,where it delivers virulence factors into host macrophages during infection.However,little is known about the molecular details as to how this occurs.Here,we provide high-resolution crystal structures of the C-terminal ATPase3 domains of EccC subunits from four different Mtb T7SS subtypes.These structures adopt a classic RecA-like a/p fold with a conserved Mg-ATP binding site.The structure of EccCbl in complex with the C-terminal peptide of EsxB identifies the location of substrate recognition site and shows how the specific signaling module XxxxMxF'for Mtb ESX-1 binds to this site resulting in a translation of the bulge loop.A comparison of all the ATPase3 structures shows there are significant differences in the shape and composition of the signal recognition pockets across the family,suggesting that distinct signaling sequences of substrates are required to be specifically recognized by different T7SSs.A hexameric model of the EccC-ATPase3 is proposed and shows the recognition pocket is located near the central substrate translocation channel.The diameter of the channel is?25-A,with a size that would allow helix-bundle shaped substrate proteins to bind and pass through.Thus,our work provides new molecular insights into substrate recognition for Mtb T7SS subtypes and also a possible transportation mechanism for substrate and/or virulence factor secretion. | Shuhui Wang Kaixuan Zhou Xiaolin Yang Bing Zhang Yao Zhao Yu Xiao Xiuna Yang Haitao Yang Luke WGuddat Jun Li Zihe Rao | 2020 | Protein & Cell2020，11，2： | 2 |
| 4 | The Rise of China's Global Middle Class in an International Context显示文摘We estimate the size of the global middle class in China and 33 other countries and analyze China’s expanding middle class in an international context.The“ghbal middle class”is defined in terms of being neither poor nor rich in the developed world.China’s global middle class has grown rapidly and has been catching up with the middle class in developed countries.By 2018 China’s global middle class constituted 25 percent of China s population;in absolute size it was nearly double the size of the global middle class in the US and was similar in size to that of Europe.Cross-country analysis of the relationship between the middle-class share of the total population and GDP per capita reveals an inverted-U pattern.China is not an outlier from the cross-country pattern but the speed with which its middle-class has expanded is unusual.The only other countries with similarly large,rapid expansions of the middle class are transition economies. | Terry Sicular Xiuna Yang Bjorn Gustafsson | 2022 | China & World Economy2022，30，1： | 1 |
| 5 | High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors显示文摘The global COVID-19 coronavirus pandemic has infected over 109 million people,leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment.Here,we screened about 1.8 million small molecules against the main protease(M^(pro))and papain like protease(PL^(pro)),two major proteases in severe acute respiratory syndrome-coronavirus 2 genome,and identified 1851M^(pro)inhibitors and 205 PL^(pro)inhibitors with low nmol/l activity of the best hits.Among these inhibitors,eight small molecules showed dual inhibition effects on both M^(pro)and PL^(pro),exhibiting potential as better candidates for COVID-19 treatment.The best inhibitors of each protease were tested in antiviral assay,with over 40%of M^(pro)inhibitors and over 20%of PL^(pro)inhibitors showing high potency in viral inhibition with low cytotoxicity.The X-ray crystal structure of SARS-CoV-2 M^(pro)in complex with its potent inhibitor 4a was determined at 1.8Åresolution.Together with docking assays,our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development. | Yi Zang Mingbo Su Qingxing Wang Xi Cheng Wenru Zhang Yao Zhao Tong Chen Yingyan Jiang Qiang Shen Juan Du Qiuxiang Tan Peipei Wang Lixin Gao Zhenming Jin Mengmeng Zhang Cong Li Ya Zhu Bo Feng Bixi Tang Han Xie Ming-Wei Wang Mingyue Zheng Xiaoyan Pan Haitao Yang Yechun Xu Beili Wu Leike Zhang Zihe Rao Xiuna Yang Hualiang Jiang Gengfu Xiao Qiang Zhao Jia Li | 2023 | Protein & Cell2023，14，1： | 0 |
| 6 | A core epitope targeting antibody of SARS-CoV-2显示文摘Dear Editor,Tremendous efforts have been made globally to develop therapeutics and prophylactics against severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)which has caused thousands of millions of infections and deaths worldwide.A series of potent neutralizing antibodies with defined epitopes targeting RBD have been recently identified with different strategies.However,being an RNA virus,the instability of the SARS-CoV-2 genome results in numerous S-protein variants with altered viral phenotypes. | Simeng Zhao Fengjiang Liu Shizhen Qiu Qiaoshuai Lan Yiran Wu Wei Xu Junzi Ke Jie Yang Xiaoyan Liu Kun Wang Hangtian Guo Shuai Xia Fangfang Zhang Jiabei Wang Xiaowen Hu Lu Lu Shibo Jiang Suwen Zhao Lianxin Liu Youhua Xie Xiuna Yang Haopeng Wang Guisheng Zhong | 2023 | Protein & Cell2023，14，1： | 0 |
| 7 | Cryo-EM structures for the Mycobacterium tuberculosis iron-loaded siderophore transporter IrtAB显示文摘The adenosine 5'-triphosphate(ATP)-binding cassette(ABC)transporter,IrtAB,plays a vital role in the replication and viability of Mycobacterium tuberculosis(Mtb),where its function is to import iron-loaded siderophores.Unusually,it adopts the canonical type IV exporter fold.Herein,we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP,ADP,or ATP analogue(AMP-PNP)at resolutions ranging from 2.8 to 3.5Å.The structure of IrtAB bound ATP-Mg2+shows a“head-to-tail”dimer of nucleotide-binding domains(NBDs),a closed amphipathic cavity within the transmembrane domains(TMDs),and a metal ion liganded to three histidine residues of IrtA in the cavity.Cryo-electron microscopy(Cryo-EM)structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB.Moreover,the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle.This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB. | Shan Sun Yan Gao Xiaolin Yang Xiuna Yang Tianyu Hu Jingxi Liang Zhiqi Xiong Yuting Ran Pengxuan Ren Fang Bai Luke WGuddat Haitao Yang Zihe Rao Bing Zhang | 2023 | Protein & Cell2023，14，6： | 0 |
| 8 | Cryo-EM snapshots of mycobacterial arabinosyltransferase complex EmbB2-AcpM2显示文摘Inhibition of Mycobacterium tuberculosis(Mtb)cell wall assembly is an established strategy for anti-TB chemotherapy.Arabinosyltransferase EmbB,which catalyzes the transfer of arabinose from the donor decaprenyl-phosphate-arabinose(DPA)to its arabinosyl acceptor is an essential enzyme for Mtb cell wall synthesis.Analysis of drug resistance mutations suggests that EmbB is the main target of the front-line anti-TB drug,ethambutol.Herein,we report the cryo-EM structures of Mycobacterium smegmatis EmbB in its'resting state'and DPA-bound'active state'.EmbB is a fifteen-transmembrane-spanning protein,assembled as a dimer.Each protomer has an associated acyl-carrier-protein(AcpM)on their cytoplasmic surface.Confor-mational changes upon DPA binding indicate an asym-metric movement within the EmbB dimer during catalysis.Functional studies have identified critical residues in substrate recognition and catalysis,and demonstrated that ethambutol inhibits transferase activity of EmbB by competing with DPA.The structures represent the first step directed towards a rational approach for anti-TB drug discovery. | Lu Zhang Yao Zha Ruogu Gao Jun Li Xiuna Yang Yan Gao Wei Zhao Sudagar S.Gurcha Natacha Veerapen Sarah M.Batt Kajelle Kaur Besra Wenqing Xu Lijun Bi Xian'en Zhang Luke W.Guddat Haitao Yang Quan Wang Gurdyal S.Besra Zihe Rao | 2020 | Protein & Cell2020，11，7： | 0 |
| 9 | Cryo-EM structures of a prokaryotic heme transporter CvdDC显示文摘DearEditor,Heme is an essential cofactor required across all kingdoms of life utilized in numerous biological processes,including cellular respiration.CydDC is a prokaryotic ATP-binding cassette(ABC)transporter required for heme assembling in respiratory cytochrome bd oxidase(Georgiou et al.,1987;Poole et al.,1989),a promising target for drug discovery(Borisov et al.,2011).CydDC is thought to play a role in maintaining an optimum periplasmic redox poise that is required for the incorporation of heme cofactors(Yamashita et al.,2014).It also suggested that CydDC is involved in heme processing by mediating glutathione/cysteine translocation(Cook and Poole,2000;Cook et al.,2002),although a role in heme translocation seems unlikely(Yamashita et al.,2014).To date,CydDC has been shown to be important for disulfide bond formation,motility,respiration,and tolerance to nitric oxide and antibiotics(Poole et al.,2019). | Chen Zhu Yanfeng Shi Jing Yu Wenhao Zhao Lingqiao Li Jingxi Liang Xiaolin Yang Bing Zhang Yao Zhao Yan Gao Xiaobo Chen Xiuna Yang Lu Zhang Luke W.Guddat Lei Liu Haitao Yang Zihe Rao Jun Li | 2023 | Protein & Cell2023，14，12： | 0 |
| 10 | DDQ as an effective p-type dopant for the hole-transport material X1 and its application in stable solid-state dye-sensitized solar cells显示文摘X1(Me O-TPD) is an inexpensive and easily synthesized π-conjugated molecule that has been used as a hole-transport material(HTM) in solid-state dye-sensitized solar cells(ssDSSCs), achieving relatively high efficiency. In this paper, we characterize the physicochemical properties of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone(DDQ) and show that it is a promising p-dopant in a spin-coating solution with X1 as the HTM. The doped ssDSSCs showed an increase in short-circuit current density from 5.38 mA cm^(-2) to7.39 mA cm^(-2), and their overall power conversion efficiency increased from 2.9% to 4.3%. Also, ssDSSCs with DDQ-doped X1 were more stable than the undoped samples, demonstrating that DDQ can act as a p-type dopant in X1 as an HTM for highly efficient, stable ssDSSCs. | Yanyun Zhang Xichuan Yang Weihan Wang Xiuna Wang Licheng Sun | 2018 | Journal of Energy Chemistry2018，27，2： | 0 |
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