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| 1 | ACPAs promote IL-1β production in rheumatoid arthritis by activating the NLRP3 inflammasome显示文摘OBJECTIVES:Anti-citrullinated protein antibodies(ACPAs)are a group of autoantibodies targeted against citrullinated proteins/peptides and are informative rheumatoid arthritis(RA)biomarkers.ACPAs also play a crucial role in RA pathogenesis,and their underlying mechanism merits investigation.METHODS:Immunohistochemical(IHC)assays were carried out to determine IL-1βlevels in ACPA+and ACPA−RA patients.PBMCderived monocytes were differentiated into macrophages before stimulation with ACPAs purified from RA patients.The localization and interaction of molecules were analyzed by confocal microscopy,co-IP,and surface plasmon resonance.RESULTS:In our study,we found that IL-1βlevels were elevated in ACPA+RA patients and that ACPAs promoted IL-1βproduction by PBMC-derived macrophages.ACPAs interacted with CD147 to enhance the interaction between CD147 and integrinβ1 and,in turn,activate the Akt/NF-κB signaling pathway.The nuclear localization of p65 promoted the expression of NLRP3 and pro-IL-1β,resulting in priming.Moreover,ACPA stimulation activated pannexin channels,leading to ATP release.The accumulated ATP bound to the P2X7 receptor,leading to NLRP3 inflammasome activation.CONCLUSIONS:Our study suggests a new hypothesis regarding IL-1βproduction in RA involving ACPAs,which may be a potential therapeutic target in RA treatment. | Xiwen Dong Zhaohui Zheng Peng Lin Xianghui Fu Fanni Li Jianli Jiang Ping Zhu | 2020 | Cellular & Molecular Immunology2020，17，3： | 11 |
| 2 | Shuganjieyu capsule increases neurotrophic factor expression in a rat model of depression显示文摘Shuganjieyu capsule has been approved for clinical treatment by the State Food and Drug Administration of China since 2008. In the clinic, Shuganjieyu capsule is often used to treat mild to moderate depression. In the rat model of depression established in this study, Shuganjieyu capsule was administered intragastrically daily before stress. Behavioral results confirmed that depressive symptoms lessened after treatment with high-dose(150 mg/kg) Shuganjieyu capsule. Immunohistochemistry results showed that high-dose Shuganjieyu capsule significantly increased phosphorylation levels of phosphorylation cyclic adenosine monophosphate response element binding protein and brain-derived neurotrophic factor expression in the medial prefrontal cortex and hippocampal CA3 area. Overall, our results suggest that in rats, Shuganjieyu capsule effectively reverses depressive-like behaviors by increasing expression levels of neurotrophic factors in the brain. | Jinhua Fu Yingjin Zhang Renrong Wu Yingjun Zheng Xianghui Zhang Mei Yang Jingping Zhao Yong Liu | 2014 | Neural Regeneration Research2014，9，5： | 10 |
| 3 | Micro/nano multiscale reinforcing strategies toward extreme high-temperature applications:Take carbon/carbon composites and their coatings as the examples显示文摘Carbon fiber reinforced carbon composites(C/Cs),are the most promising high-temperature materials and could be widely applied in aerospace and nucleation fields,owing to their superior performances.However,C/Cs are very susceptible to destructive oxidation and thus fail at elevated temperatures.Though matrix modification and coating technologies with Si-based and ultra-high temperature ceramics(UHTCs)are valid to enhance the oxidation/ablation resistance of C/Cs,it’s not sufficient to satisfy the increasing practical applications,due to the inherent brittleness of ceramics,mismatch issues between coatings and C/C substrates,and the fact that carbonaceous matrices are easily prone to high-temperature oxidation.To effectively solve the aforementioned problems,micro/nano multiscale reinforcing strategies have been developed for C/Cs and/or the coatings over the past two decades,to fabricate C/Cs with high strength and excellent high-temperature stability.This review is to systematically summarize the most recent major and important advancements in some micro/nano multiscale strategies,including nanoparticles,nanowires,carbon nanotubes/fibers,whiskers,graphene,ceramic fibers and hybrid micro/nano structures,for C/Cs and/or the coatings,to achieve high-temperature oxidation/ablation-resistant C/Cs.Finally,this review is concluded with an outlook of major unsolved problems,challenges to be met and future research advice for C/Cs with excellent comprehensive mechanical-thermal performance.It’s hoped that a better understanding of this review will be of high scientific and industrial interest,since it provides unusual and feasible new ideas to develop potential and practical C/Cs with improved high-temperature mechanical and oxidation/ablation-resistant properties. | Qiangang Fu Pei Zhang Lei Zhuang Lei Zhou Jiaping Zhang Jie Wang Xianghui Hou Ralf Riedel Hejun Li | 2022 | Journal of Materials Science & Technology2022，，1： | 7 |
| 4 | CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta,alpha,beta,and gamma显示文摘SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape,compromising the effectiveness of existing vaccines and neutralizing antibodies.An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants.Here,we identified CD147 as a universal receptor for SARS-CoV-2 and its variants.Meanwhile,Meplazeumab,a humanized anti-CD147 antibody,could block cellular entry of SARS-CoV-2 and its variants-alpha,beta,gamma,and delta,with inhibition rates of 68.7,75.7,52.1,52.1,and 62.3%at 60μg/ml,respectively.Furthermore,humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants,alpha and beta.When infected,these mice developed exudative alveolar pneumonia,featured by immune responses involving alveoli-infiltrated macrophages,neutrophils,and lymphocytes and activation of IL-17 signaling pathway.Mechanistically,we proposed that severe COVID-19-related cytokine storm is induced by a'spike protein-CD147-CyPA signaling axis':Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway,which further induced expression of cyclophilin A(CyPA);CyPA reciprocally bound to CD147 and triggered MAPK pathway.Consequently,the MAPK pathway regulated the expression of cytokines and chemokines,which promoted the development of cytokine storm.Importantly,Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants.Therefore,our findings provided a new perspective for severe COVID-19-related pathogenesis.Furthermore,the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment. | Jiejie Geng Liang Chen Yufeng Yuan Ke Wang Youchun Wang Chuan Qin Guizhen Wu Ruo Chen Zheng Zhang Ding Wei Peng Du Jun Zhang Peng Lin Kui Zhang Yongqiang Deng Ke Xu Jiangning Liu Xiuxuan Sun Ting Guo Xu Yang Jiao Wu Jianli Jiang Ling Li Kun Zhang Zhe Wang Jing Zhang Qingguo Yan Hua Zhu Zhaohui Zheng Jinlin Miao Xianghui Fu Fengfan Yang Xiaochun Chen Hao Tang Yang Zhang Ying Shi Yumeng Zhu Zhuo Pei Fei Huo Xue Liang Yatao Wang Qingyi Wang Wen Xie Yirong Li Mingyan Shi Huijie Bian Ping Zhu Zhi-Nan Chen | 2021 | Signal Transduction and Targeted Therapy2021，6，10： | 6 |
| 5 | Analysis of uterine CD49a^(+) NK cell subsets in menstrual blood reflects endometrial status and association with recurrent spontaneous abortion显示文摘Maternal uterine immune cells,especially natural killer(NK)cells,are important for successful pregnancy,and an abnormal number or function of uterine NK cells is closely correlated with an impaired endometrial environment and miscarriage.However,there are currently no noninvasive testing methods using reliable indicators that accurately predict uterine changes leading to miscarriage.Here,we confirmed that before implantation,menstrual blood(MB)from healthy donors had 70%CD49a^(+)tissue-resident NK(trNK)cells,the majority of which were CD49a^(+)Eomes+NK cells.Importantly,MB from patients with recurrent spontaneous abortion(RSA)had many fewer CD49a^(+)trNK cells than MB from controls.Analysis of uNK cell populations in MB may better predict an abnormal endometrial environment associated with miscarriage than peripheral blood(PB)analysis.Therefore,we suggest using MB-and CD49a-related markers as a promising noninvasive way to evaluate endometrial status. | Xianhong Tong Min Gao Xianghui Du Fangting Lu Limin Wu Haiming Wei Binqing Fu | 2021 | Cellular & Molecular Immunology2021，18，7： | 2 |
| 6 | Norovirus P particle-based tau vaccine-generated phosphorylated tau antibodies markedly ameliorate tau pathology and improve behavioral deficits in mouse model of Alzheimer’s disease显示文摘Dear Editor,Currently,there are no FDA-approved disease-modifying therapies that can prevent,halt,or reverse Alzheimer's disease(AD).As the unsatisfactory of amyloid-p-targeted treatment in recent years,development of Tau-targeted active immunotherapy takes much concern.1 Tau protein,a major microtubule-associated protein in the nervous system,was found to be abnormally hyperphosphorylated at six epitopes:Ser396/404,Ser202,Thr205,Ser238,and Ser262 in AD patients.2 Hence,immunotherapy targeting more highly-expressed phosphorylated Tau(pTau)species may induce a sufficient pool of pTau antibodies to eliminate pathological tau and elicit cognitive improvement. | Yao Sun Yongqing Guo Xuejian Feng Lu Fu Yayuan Zheng Yue Dong Yong Zhang Xianghui Yu' Wei Kong Hui Wu | 2021 | Signal Transduction and Targeted Therapy2021，6，3： | 1 |
| 7 | Soot oxidation via CuO doped CeO2 catalysts prepared using coprecipitation and citrate acid complex-combustion synthesis显示文摘 | Fu Mingli Yue Xianghui Ye Daiqi | 2010 | Catalysts Today2010，，3： | 1 |
| 8 | miR‐194 is a marker of hepatic epithelial cells and suppresses metastasis of liver cancer cells in mice显示文摘 | Zhipeng Meng Xianghui Fu Xiaosong Chen Samuel Zeng Yan Tian Richard Jove Rongzhen Xu Wendong Huang | 2010 | Hepatology2010，，6： | 1 |
| 9 | ELANE:an emerging lane to selective anticancer therapy显示文摘Recently,Cui et al.1 revealed that neutrophil elastase(ELANE)can selectively kill a wide range of cancer cells while sparing proximal non-cancer cells and significantly attenuate tumorigenesis,suggesting a promising selective and broad anticancer strategy. | Boqiang Peng Jiankun Hu Xianghui Fu | 2021 | Signal Transduction and Targeted Therapy2021，6，11： | 1 |
| 10 | Two forms of the membrane-bound state of the first C2 domain (C2A) of synaptotagminⅠand calcium-triggered membrane insertion显示文摘The synaptic vesicle protein synaptotagminⅠ (sytⅠ) is a vesicle transmembrane protein present in synap-tic vesicles, which has been proposed as the Ca2+ sensor that regulates secretion. The C2A domain is the membrane proximal part of its cytoplasmic domain. The interaction between C2A and lipid bilayer has been considered to be essential for triggering neurotransmitter release. In the pre-sent work, the measurements of membrane surface tension and surface concentration showed that the C2A domain of sytⅠexhibited two membrane-bound states: the surface adsorption state and the membrane insertion state. The sur-face absorption state formed in a Ca2+-independent manner with lower affinity, while the membrane insertion state formed with high affinity was only found in the presence of Ca2+. Both the Ca2+-independent and Ca2+-dependent sytⅠ- membrane interactions required anionic phospholipids, such as phosphatidylserine (PS). When expressed into rat pheo-chromocytoma (PC12) cells and human embryonic kidney (HEK-293) cells, as demonstrated by immunofluorescence staining and subcellular fractionation, most of the C2A was found at the plasma membrane, even when the cells were depleted of Ca2+ by incubation with EGTA. These results suggested a new molecular mechanism of sytⅠas a Ca2+ sensor in membrane fusion. Ca2+-independent surface ad-sorption might attach sytⅠto the release site during the docking or priming step. When intracellular Ca2+ increased, sytⅠtriggered the neurotransmitter release following the Ca2+-dependent penetration into the target membrane. | HE Yuhong, LI Xianghui, WANG Fu, XUE Yi & SUI Senfang Department of Biological Sciences & Biotechnology, State Key Labora-tory of Biomembrane, Tsinghua University, Beijing 100084, China | 2003 | Chinese Science Bulletin2003，48，17： | 0 |
| 11 | Correction to:Norovirus P particle-based tau vaccinegenerated phosphorylated tau antibodies markedly ameliorate tau pathology and improve behavioral deficits in mouse model of Alzheimer’s disease显示文摘In the process of collating the published data,the authors noticed one inadvertent mistake occurred during the production process in Fig.1u that needs to be corrected.1 The authors mistakenly placed the wrong western blot figure for the level of pTauS404 in the urea fraction of mice from the onset cohort in Fig.lu.The correct data are provided as follows.The key findings of the article are not affected by these corrections.The original article has been corrected. | Yao Sun Yongqing Guo Xuejian Feng Lu Fu Yayuan Zheng Yue Dong Yong Zhang Xianghui Yu Wei Kong Hui Wu | 2021 | Signal Transduction and Targeted Therapy2021，6，7： | 0 |
| 12 | CD98-induced CD147 signaling stabilizes the Foxp3 protein to maintain tissue homeostasis显示文摘Regulatory T cell(Treg)stability is necessary for the proper control of immune activity and tissue homeostasis.However,it remains unclear whether Treg stability must be continually reinforced or is established during development under physiological conditions.Foxp3 has been characterized as a central mediator of the genetic program that governs Treg stability.Here,we demonstrate that to maintain Foxp3 protein expression,Tregs require cell-to-cell contact,which is mediated by the CD147-CD98 interaction.As Tregs are produced,CD147,which is expressed on their surface,is stimulated by CD98,which is widely expressed in the physiological environment.As a result,CD147’s intracellular domain binds to CDK2 and retains it near the membrane,leading to Foxp3 dephosphorylation and the prevention of Foxp3 degradation.In addition,the optimal distribution of Foxp3+Tregs under both pathological and physiological conditions depends on CD98 expression.Thus,our study provides direct evidence that Foxp3-dependent Treg stability is reinforced in the periphery by the interaction between CD147 and CD98 in the surrounding environment.More importantly,Tregs with high CD147 expression effectively inhibit inflammatory responses and maintain Foxp3 stability,which has guiding significance for the application of Tregs in immunotherapy. | JieJie Geng Ruo Chen Feng-fan Yang Peng Lin Yu-meng Zhu Xianghui Fu Ke Wang Zhuan Feng Jiao Wu Hai Zhang Qi-jing Li Zhi-Nan Chen Ping Zhu | 2021 | Cellular & Molecular Immunology2021，18，12： | 0 |
| 13 | Reduction of ice adhesion on nanostructured and nanoscale slippery surfaces显示文摘Ice nucleation and accretion on structural surfaces are sources of major safety and operational concerns in many industries including aviation and renewable energy.Common methods for tackling these are active ones such as heating,ultrasound,and chemicals or passive ones such as surface coatings.In this study,we explored the ice adhesion properties of slippery coated substrates by measuring the shear forces required to remove a glaze ice block on the coated substrates.Among the studied nanostructured and nanoscale surfaces[i.e.,a superhydrophobic coating,a fluoropolymer coating,and a polydimethylsiloxane(PDMS)chain coating],the slippery omniphobic covalently attached liquid(SOCAL)surface with its flexible polymer brushes and liquid-like structure significantly reduced the ice adhesion on both glass and silicon surfaces.Further studies of the SOCAL coating on roughened substrates also demonstrated its low ice adhesion.The reduction in ice adhesion is attributed to the flexible nature of the brush-like structures of PDMS chains,allowing ice to detach easily. | Luke Haworth Deyu Yang Prashant Agrawal Hamdi Torun Xianghui Hou Glen McHale Yongqing Fu | 2023 | Nanotechnology and Precision Engineering2023，6，1： | 0 |
| 14 | Role of Intracellular Distribution of Feline and Bovine SAMHD1 Proteins in Lentiviral Restriction显示文摘Human SAMHD1(h SAM)restricts lentiviruses at the reverse transcription step through its d NTP triphosphohydrolase(d NTPase)activity.Besides humans,several mammalian species such as cats and cows that carry their own lentiviruses also express SAMHD1.However,the intracellular distribution of feline and bovine SAMHD1(f SAM and b SAM)and its significance in their lentiviral restriction function is not known.Here,we demonstrated that f SAM and b SAM were both predominantly localized to the nucleus and nuclear localization signal(11KRPR14)-deleted f SAM and b SAM relocalized to the cytoplasm.Both cytoplasmic f SAM and b SAM retained the antiviral function against different lentiviruses and cytoplasmic f SAM could restrict Vpx-encoding SIV and HIV-2 more efficiently than its wild-type(WT)protein as cytoplasmic h SAM.Further investigation revealed that cytoplasmic f SAM was resistant to Vpx-induced degradation like cytoplasmic h SAM,while cytoplasmic b SAM was not,but they all demonstrated the same in vitro d NTPase activity and all could interact with Vpx as their WT proteins,indicating that cytoplasmic h SAM and f SAM can suppress more SIV and HIV-2 by being less sensitive to Vpx-mediated degradation.Our results suggested that f SAM-and b SAM-mediated lentiviral restriction does not require their nuclear localization and that f SAM shares more common features with h SAM.These findings may provide insights for the establishment of alternative animal models to study SAMHD1 in vivo. | Chu Wang Lina Meng Jialin Wang Kaikai Zhang Sizhu Duan Pengyu Ren Yingzhe Wei Xinyu Fu Bin Yu Jiaxin Wu Xianghui Yu | 2021 | Virologica Sinica2021，36，5： | 0 |
| 15 | A folic acid-decorated nanoparticles loaded JQ1 for oral squamous cell carcinoma therapy显示文摘Oral squamous cell carcinoma(OSCC)is known as one of the most malignant tumors with high recurrence and fatality rate.The poor tumor-targeting ability of traditional chemotherapeutic drugs has been a grand challenge for anti-OSCC therapy.Beyond that,a large quantity of tumor associated macrophages in OSCC tissues further diminish the anti-tumor effects of these drugs.Therefore,we produced a therapeutic nano drug delivery system(FA-PEG-PLA-JQ1)through encapsulating JQ1[a small-molecule inhibitor of bromodomain containing protein 4(BRD4)]into the folic acid(FA)-modified nanoparticle(PEG-PLA),which could prolong the half-life of JQ1 and target the tumor tissues.And then,JQ1 released from this nanoparticle could prevent OSCC growth inducing tumor cell apoptosis,inhibiting tumor angiogenesis and the polarization of M2 type macrophages.In conclusion,our date demonstrated the therapeutic benefits of FA-PEG-PLA-JQ1 against OSCC in vivo or in vitro,which could be a novel treatment strategy for OSCC in coming days. | Dequan Zeng Zhongkai Ma Xin Zan Ting Luo Xiang Wang Xiang Gao Xianghui Fu | 2024 | Chinese Chemical Letters2024，35，3： | 0 |
| 16 | Ferritin,heavy polypeptide 1 interacts with fragile X-related protein 1显示文摘Fragile X-related protein 1(FXR1P) is a member of the FXR gene family,which also includes fragile X mental retardation protein and fragile X-related protein 2(FXR2P).To understand the functions of FXR1P,we screened FXR1P-interacting proteins using a yeast two-hybrid system.FXR1P was fused to pGBKT7 and used as the bait to screen a human fetal brain cDNA library.This screening revealed 10 FXR1P-interacting proteins including FTH1.FTH1 encodes Homo sapiens ferritin,heavy polypeptide 1.The interaction between FXR1P and FTH1 was confirmed by retesting in yeast using both a β-galactosidase assay and growth studies on selective media.A co-immunoprecipitation assay in mammalian cells further confirmed the FXR1P/FTH1 interaction.Moreover,the results revealed that FTH1 colocalized with FXR1P in the cytoplasm around the nucleus in mammalian cells.The present findings suggest that FXR1P plays an important role in iron metabolism in the brain by interacting with FTH1.This provides clues for elucidating the relationship between FXR1P function and fragile X syndrome. | Yun Ma Shuya He Yang Yang Qiong Chen Weichun Xiao Binyuan Li Jiao Su Xianghui Fu | 2011 | Neural Regeneration Research2011，6，10： | 0 |
| 17 | CD147 contributes to SARS-CoV-2-induced pulmonary fibrosis显示文摘COVID‐19 patients can develop clinical and histopathological features associated with fibrosis,but the pathogenesis of fibrosis remains poorly understood.CD147 has been identified as a universal receptor for SARS-CoV-2 and its variants,which could initiate COVID-19-related cytokine storm.Here,we systemically analyzed lung pathogenesis in SARS-CoV-2-and its delta variant-infected humanized CD147 transgenic mice.Histopathology and Transmission Electron Microscopy revealed inflammation,fibroblast expansion and pronounced fibrotic remodeling in SARS-CoV-2-infected lungs.Consistently,RNA-sequencing identified a set of fibrosis signature genes.Furthermore,we identified CD147 as a crucial regulator for fibroblast activation induced by SARS-CoV-2.We found conditional knockout of CD147 in fibroblast suppressed activation of fibroblasts,decreasing susceptibility to bleomycin-induced pulmonary fibrosis.Meplazumab,a CD147 antibody,was able to inhibit the accumulation of activated fibroblasts and the production of ECM proteins,thus alleviating the progression of pulmonary fibrosis caused by SARS-CoV-2.In conclusion,we demonstrated that CD147 contributed to SARS-CoV-2-triggered progressive pulmonary fibrosis and identified CD147 as a potential therapeutic target for treating patients with post-COVID-19 pulmonary fibrosis. | Jiao Wu Liang Chen Chuan Qin Fei Huo Xue Liang Xu Yang Kui Zhang Peng Lin Jiangning Liu Zhuan Feng Jiansheng Zhou Zhuo Pei Yatao Wang Xiu-Xuan Sun Ke Wang Jiejie Geng Zhaohui Zheng Xianghui Fu Man Liu Qingyi Wang Zheng Zhang Huijie Bian Ping Zhu Zhi-Nan Chen | 2022 | Signal Transduction and Targeted Therapy2022，7，12： | 0 |
| 18 | Crystal structure and catalytic mechanism of the MbnBC holoenzyme required for methanobactin biosynthesis显示文摘Methanobactins(Mbns)are a family of copper binding peptides involved in copper uptake by methanotrophs,and are potential therapeutic agents for treating diseases characterized by disordered copper accumulation.Mbns are produced via modification of MbnA precursor peptides at cysteine residues catalyzed by the core biosynthetic machinery containing MbnB,an iron-dependent enzyme,and MbnC.However,mechanistic details underlying the catalysis of the MbnBC holoenzyme remain unclear.Here,we present crystal structures of MbnABC complexes from two distinct species,revealing that the leader peptide of the substrate MbnA binds MbnC for recruitment of the MbnBC holoenzyme,while the core peptide of MbnA resides in the catalytic cavity created by the MbnB-MbnC interaction which harbors a unique tri-iron cluster.Ligation of the substrate sulfhydryl group to the tri-iron center achieves a dioxygen-dependent reaction for oxazolone thioamide installation.Structural analysis of the MbnABC complexes together with functional investigation of MbnB variants identifed a conserved catalytic aspartate residue as a general base required for MbnBC-mediated MbnA modifcation.Together,our study reveals the similar architecture and function of MbnBC complexes from different species,demonstrating an evolutionarily conserved catalytic mechanism of the MbnBC holoenzymes. | Chao Dou Zhaolin Long Shoujie Li Dan Zhou Ying Jin Li Zhang Xuan Zhang Yanhui Zheng Lin Li Xiaofeng Zhu Zheng Liu Siyu He Weizhu Yan Lulu Yang Jie Xiong Xianghui Fu Shiqian Qi Haiyan Ren She Chen Lunzhi Dai Binju Wang Wei Cheng | 2022 | Cell Research2022，32，3： | 0 |
| 19 | Infrared spectra study associated with hydrogen impurity in low pressure CVD diamond films显示文摘The infrared absorbance peaks at 2 852.4, 2 924.3, 2963.0 and 3 034.9 cm-1 have been observed in diamond films made by the direct current arc discharge plasma chemical vapor deposition. Three former absorbance peaks have been assigned to C-H stretching in SP3 configuration, 3 034.9 cm-1 has been assigned to C-H stretching in SP2 configuration. The | Huifang Fu Xianghui Zhang Entao Yan Shunsheng Liu | 1999 | Chinese Science Bulletin1999，44，16： | 0 |
| 20 | Deciphering the regulatory and catalytic mechanisms of an unusual SAM-dependent enzyme显示文摘S-adenosyl-1-methionine(SAM)-dependent enzymes regulate various disease-related behaviors in all organisms.Recently,the leporin biosynthesis enzyme LepI,a SAM-dependent enzyme,was reported to catalyze pericyclic reactions in leporin biosynthesis;however,the mechanisms underlying LepI activation and catalysis remain unclear.This study aimed to investigate the molecular mechanisms of LepI.Here,we reported crystal structures of LepI bound to SAM/5′-deoxy-5′-(methylthio)adenosine(MTA),S-adenosyl-homocysteine(SAH),and SAM/substrate states.Structural and biochemical analysis revealed that MTA or SAH inhibited the enzyme activities,whereas SAM activated the enzyme.The analysis of the substrate-bound structure of LepI demonstrated that this enzymatic retro-Claisen rearrangement was primarily driven by three critical polar residues His133,Arg197,Arg295 around the active site and assisted by SAM with unclear mechanism.The present studies indicate that the unique mechanisms underlying regulatory and catalysis of the unusual SAM-dependent enzyme LepI,not only strengthening current understanding of the fundamentally biochemical catalysis,but also providing novel insights into the design of SAM-dependent enzyme-specific small molecules. | Qiu Sun Yuehong Hu Yijun Gu Jiangkun Huang Jun He Lan Luo Yi Yang Shuo Yin Chao Dou Tianqi Wang Xianghui Fu Ling He Shiqian Qi Xiaofeng Zhu Shengyong Yang Xiawei Wei Wei Cheng | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 0 |
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