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tyrosine aminotransferase: biochemical and structural properties and molecular dynamics simulations

Protein & Cell 2010年第11期1卷 1023-1032页

作者： Prajwalini Mehere Qian Han Justin A.Lemkul Christopher J.Vavricka Howard Robinson David R.Bevan Jianyong Li Department of Biochemistry Virginia TechBlacksburgVA 24061USA CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Biology Department Brookhaven National LaboratoryUptonNY 11973USA

tyrosine aminotransferase(TAT)catalyzes the transamination of tyrosine and other aromatic amino *** enzyme is thought to play a role in tyrosinemia type II,hepatitis and hepatic carcinoma *** objective of this study is to investigate its biochemical and structural characteristics and substrate specificity in order to provide insight regarding its involvement in these *** TAT(mTAT)was cloned from a mouse cDNA library,and its recombinant protein was produced using Escherichia coli cells and purified using various chromatographic *** recombinant mTAT is able to catalyze the transamination of tyrosine usingα-ketoglutaric acid as an amino group acceptor at neutral *** enzyme also can use glutamate and phenylalanine as amino group donors and p-hydroxyphenylpyruvate,phenylpyruvate and alpha-ketocaproic acid as amino group *** macromolecular crystallography we have determined the mTAT crystal structure at 2.9Å*** crystal structure revealed the interaction between the pyridoxal-5′-phosphate cofactor and the enzyme,as well as the formation of a disulphide *** detection of disulphide bond provides some rational explanation regarding previously observed TAT inactivation under oxidative conditions and reactivation of the inactive TAT in the presence of a reducing *** dynamics simulations using the crystal structures of Trypanosoma cruzi TAT and human TAT provided further insight regarding the substrate-enzyme interactions and substrate *** biochemical and structural properties of TAT and the binding of its cofactor and the substrate may help in elucidation of the mechanism of TAT inhibition and activation.

关键词： tyrosine aminotransferase crystal structure substrate specificity tyrosine tyrosinemia

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tyrosine phosphatase SHP2 in ovarian granulosa cells balances follicular development by inhibiting PI3K/AKT signaling

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Journal of Molecular Cell Biology 2022年第7期14卷 23-36页

作者： Xiaoli Wei Lanping Zheng Yingpu Tian Haibin Wang Youqiang Su Gensheng Feng Chao Wang Zhongxian Lu School of Pharmaceutical Sciences State Key Laboratory of Cellular Stress BiologyXiamen UniversityXiamen 361005China Fujian Provincial Key Laboratory of Reproductive Health Research Medical College of Xiamen UniversityXiamen 361102China State Key Laboratory of Agrobiotechnology College of Biological SciencesChina Department of Pathology Division of Biological SciencesUniversity of California at San DiegoLa JollaCA 92093USA State Key Laboratory of Agrobiotechnology College of Biological SciencesChina Agricultural UniversityBeijing 100193China

In mammals,the growth and maturation of oocytes within growing follicles largely depends on ovarian granulosa cells(GCs)in response to gonadotropin *** signals have been shown to regulate GC proliferation and ***,whether the tyrosine phosphatase SHP2 is involved remains *** this study,we identified the crucial roles of SHP2 in modulating GC proliferation and *** production of both mature oocytes and pups was increased in mice with Shp2 specifically deleted in ovarian GCs via ***2 deletion simultaneously promoted GC proliferation and inhibited GC ***,Shp2 deficiency promoted,while Shp2 overexpression inhibited,the proliferation of cultured primary mouse ovarian GCs and the human ovarian granulosa-like tumor cell line KGN in ***2 deficiency promoted follicule-stimulating hormone(FSH)-activated phosphorylation of AKT in ***2 deficiency reversed the inhibitory effect of hydrogen peroxide(H_(2)O_(2))on AKT activation in KGN cells.H_(2)O_(2) treatment promoted the interaction between SHP2 and the p85 subunit of PI3K in KGN ***,SHP2 in GCs may act as a negative modulator to balance follicular development by suppressing PI3K/AKT *** novel function of SHP2 in modulating proliferation and apoptosis of GCs provides a potential therapeutic target for the clinical treatment of follicle developmental dysfunction.

关键词： tyrosine phosphatase SHP2 granulosa cell follicular development PI3K/AKT signaling

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Radioiodinated tyrosine based carbon dots with efficient renal clearance for single photon emission computed tomography of tumor

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Nano Research 2019年第12期12卷 3037-3043页

作者： Nian Liu Yiyue Shi Jingru Guo Hai Li Qiang Wang Menglin Song Zhiyuan Shi Le He Xinhui Su Jin Xie Xiaolian Sun State Key Laboratory of Natural Medicines Key Laboratory of Drug Quality Control and PharmacovigilanceDepartment of Pharmaceutical AnalysisChina Pharmaceutical UniversityNanjing 210009China Institute of Biological and Medical Imaging Helmholtz Zentrum Miinchen and Technische Universitat MiinchenNeuherberg 85764Germany State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics&Center for Molecular Imaging and Translational Medicine School of Public HealthXiamen UniversityXiamen 361005China Institute of Functional Nano&Soft Materials(FUNSOM) Jiangsu Key Laboratory for Carbon-Based Functional Materials&DevicesSoochow UniversitySuzhou 215123China Department of Nuclear Medicine Zhongshan Hospital Xiamen UniversityXiamen 361004China Department of Chemistry Bio-Imaging Research CenterUniversity of GeorgiaAthensGeorgia 30602USA

Nan oparticles with effective tumor accumulation and efficient renal clearance have attracted significant interests for clinical *** 2.5 nm tyrosine based carbon dots(TCDs)with phenolic hydroxyl groups on the surface for directly 125I *** 125I labeledpolyethylene glycol(PEG)functionalized TCDs(125I-TCDPEGs)showed excellent radiochemical stability both in vitro and in *** to theenhanced permeability and retentio n effect,these 125I-TCDPEGs demonstrated a tumor accumulatio n around 4%-5%of the injected doseper gram(ID/g)for U87MG,4T1,HepG2 and MCF7 tumor-bearing mice at 1 h ***,the 125I-TCDPEGs also could befast renally excreted,with less than 0.6%ID/g left in the liver and spleen within 24 *** radioactive carb on dots not only can be used forcellular fluorescence imaging due to their intrinsic optical property,but are also effective single photon emission computed tomography(SPECT)imaging agents for *** with their excellent biocompatibility and stability,we anticipate these 125I-TCDPEGs of great potential for earlytumor diagnosis in *** more,our TCDPEGs are also proved to be feasible carriers for other iodine isotopes such as 127I and 131I fordifferent biomedical application.

关键词： radioiodination tyrosine based carbon dots single photon emissionrenal clearance

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Quanti?cation of tyrosine Hydroxylase and Erb B4 in the Locus Coeruleus of Mood Disorder Patients Using a Multispectral Method to Prevent Interference with Immunocytochemical Signals by Neuromelanin

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Neuroscience Bulletin 2019年第2期35卷 205-215页

作者： Lei Guo Jochem StormmesAND Zheng Fang Qingbin Zhu Rawien Balesar Joop van Heerikhuize Arja Sluiter Dick Swaab Ai-Min Bao Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital Institute of NeuroscienceNHC and CAMS Key Laboratory of Medical NeurobiologyZhejiang University School of Medicine Netherlands Institute for Neuroscience Institute of the Royal Netherlands Academy of Arts and Sciences Department of Neurology Sir Run Run Shaw HospitalZhejiang University School of Medicine

The locus coeruleus(LC) has been studied in major depressive disorder(MDD) and bipolar disorder(BD). A major problem of immunocytochemical studies in the human LC is interference with the staining of the immunocytochemical end-product by the omnipresent natural brown pigment neuromelanin. Here, we used a multispectral method to untangle the two colors: blue immunocytochemical staining and brown *** found significantly increased tyrosine hydroxylase(TH) in the LC of MDD patients—thus validating the method—but not in BD patients, and we did not find significant changes in the receptor tyrosine-protein kinase ErbB4 in the LC in MDD or BD patients. We observed clear co-localization of ErbB4, TH, and neuromelanin in the LC neurons. The different stress-related molecular changes in the LC may contribute to the different clinical symptoms in MDD and BD.

关键词： Major depressive disorder Bipolar disorder tyrosine hydroxylase ErbB4 Locus coeruleus

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In-situ electro-polymerization of L-tyrosine enables ultrafast,long cycle life for lithium metal battery

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Chinese Chemical Letters 2023年第5期34卷 561-566页

作者： Zihao Chu Sidong Zhuang Jiahui Lu Jiabao Li Chengyin Wang Tianyi Wang College of Chemistry and Chemical Engineering Yangzhou UniversityYangzhou 225002China

The growth of dendrites in the lithium(Li)metal anode hinders the commercialization of lithium metal batteries(LMBs).Electrolyte additives have proved to be an effective way to solve the problem of dendrites and improve the coulombic ***,we propose a strategy of using L-tyrosine(L-Tyr)as an additive to protect the lithium metal anode in situ,where L-Tyr can be electropolymerized in situ to form an ordered array of nanosheets on the surface of the lithium metal anode to uniformly deposit lithium *** the same time,the addition of L-Tyr changed the structure of the solvent in the electrolyte,because the carboxyl group on L-Tyr make DME form hydrogen bonds ***,the reduction of free DME makes more TFSI-involved in the formation of the SEI film on the electrode surface,which increases the proportion of LiF in the SEI *** 2 wt%L-Tyr,Li||Li symmetric cells superior cycle stability in ether electrolytes,Li|Cu cells y improved stability up to 200 cycles with an average CE of 93.1%in ether electrolytes and Li||Li_(4)Ti_(5)O_(12)(LTO)demonstrated an excellent cycling capabilitie with 119 mAh/g capacity retention by the 5000^(th)cycle.

关键词： Lithium metal battery tyrosine In situ Eelectropolymerization lithium dendrite

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CRISPR/Cas9-mediated tyrosine hydroxylase knockout resulting in larval lethality in Agrotis ipsilon

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Insect Science 2018年第6期25卷 1017-1024页

作者： Yang Yang Yao-Hui Wang Xi-En Chen Di Tian Xia Xu Kai Li Yong-Ping Huang Lin He School of Life Science East China Normal UniversityShanghaiChina Key Laboratory of Insect Developmental and Evolutionary Biology Institute of Plant Physiology and EcologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina Hubei Key Laboratory of Insect Resource Application and Sustainable Pest Control College of Plant Science &TechnologyHuazhong Agricultural UniversityWuhanChina

tyrosine hydroxylase (TH)is involved in insect melanin and the catecholamine biosynthesis *** as an enzyme catalyzing the conversion of tyrosine to 3,4- dihydroxyphenylalanine is the first step reaction in the *** TH has been proven to affect the pigmentation of the epidermis and development in many insects,there is no report about physiological function of the THgene inAgrotis *** we cloned the TH gene from ***-quantitative real-time polymerase chain reaction (PCR) analysis showed that AiTH was expressed at all development ***,its high expression levels in the head and epidermis suggest that it is mainly related to pigment deposition and insect ***,we used the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9system to target the AiTH gene:deletion events were detected at the target *** with the control group,a few mutants with the phenomenon of narrowing in the egg shell and embryos can develop but cannot hatch;the other hatched embryos were seriously dehydrated after hatching and died within the first *** real-time PCR analysis revealed that THwas down-regulated ***,our work demonstrated thatAiTHplays an important role in growth and development of newly hatched larvae;meanwhile,it would be a promising target to explore a control strategy for ***.

关键词： Agrotis ipsilon CRISPR/Cas9system larvae lethal tyrosine hydroxylase

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Exploration of Zinc(II)Complexes as Potent Inhibitors Against Protein tyrosine Phosphatase IB

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Chemical Research in Chinese Universities 2019年第2期35卷 186-192页

作者： LI Xinhua YUAN Caixia LU Liping ZHU Miaoli XING Shu FU Xueqi Key Laboratory of Chemical Biology and Molecular Engineefing Ministry of EducationInstitute of Molecular ScienceShanxi UniversityTaiyuan 030006P.R.China Edmond H. Fischer Signal Transduction Laboratory College of Life SciencesJilin UniversityChangchun 130012P.R.China

Although protein tyrosine phosphatases(PTPs)do not contain any metals,their activities can be inhibited by some metal *** we investigated the inhibition of two zinc complexes with Schiff base ligands against PTPs activity to explore their effect on the cellular *** has been found that they are potent inhibitors against four recombinant PIPs5 including protein tyrosine phosphatase 1B(PTP1B),T cell protein tyrosine phosphatase(TCPTP),megakaryocyte protein tyrosine phosphatase 2(PTP-MEG2)S and Src-homology phosphatase 1(SHP-1),with exception of Src-homology phosphatase 2(SHP-2).Moreover,tlaey showed moderate selective inhibition against PTP1B with the IG50 values of 0.15 and 0.36μmol/***,the complexes also inhibited cellular phosphatase activities *** the inhibitory potency over PTPs mediated by the zinc ion,we found that zinc complexes might be easily developed into potent and selective inhibitors against certain PTP by rationally modifying the organic ligands moieties.

关键词： Zinc complex Schiff base Protein tyrosine phosphatase Inhibitor

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Detection of tyrosine,trace metals and nutrients in cow dung:the environmental significance in soil and water environments

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Acta Geochimica 2018年第4期37卷 632-638页

作者： Khan M.G.Mostofa Longlong Li Congqiang Liu Institute of Surface-Earth System Science Tianjin University State Key Laboratory of Environmental Geochemistry Institute of GeochemistryChinese Academy of Sciences

This study examined the dissolved organic matter(DOM) components of cow dung using a combination of fluorescence(excitation–emission matrix,EEM)spectroscopy and parallel factor(PARAFAC) modelling along with eleven trace metals using ICP-MS and nutrients(NH_4^+ and NO_3^-) using an AA3 auto analyser. EEM–PARAFAC analysis demonstrated that cow dung predominantly contained only one fluorescent DOM component with two fluorescence peaks(Ex/Em=275/311 nm and Ex/Em=220/311 nm),which could be denoted as tyrosine by comparison with its standard. Occurrence of tyrosine can be further confirmed by the FTIR spectra. Trace metals analysis revealed that Na,K and Mg were significantly higher than Ca,Fe,Mn,Zn Sr,Cu,Ni and Co. The NH_4^+ concentrations were substantially higher than NO_3^-.These results thus indicate that the dissolved components of the cow dung could be useful for better understanding its future uses in various important purposes.

关键词： Cow dung Excitation-emission matrix (EEM)spectroscopy Parallel factor (PARAFAC) modelling tyrosine Trace metals

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Protein tyrosine phosphatase 1B inhibitory activities of ursane-type triterpenes from Chinese raspberry, fruits of Rubus chingii

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Chinese Journal of Natural Medicines 2019年第1期17卷 15-21页

作者： ZHANG Xiang-Yu LI Wei WANG Jian LI Ning CHENG Mao-Sheng KOIKE Kazuo Key Laboratory of Structure-Based Drug Design&Discovery Ministry of EducationShenyang Pharmaceutical University School of Pharmaceutical Engineering Shenyang Pharmaceutical University Faculty of Pharmaceutical Sciences Toho University

Protein tyrosine phosphatase 1 B(PTP1 B) has led to an intense interest in developing its inhibitors as anti-diabetes, anti-obesity and anti-cancer agents. The fruits of Rubus chingii(Chinese raspberry) were used as a kind of dietary traditional Chinese medicine. The methanolic extract of R. chingii fruits exhibited significant PTP1 B inhibitory activity. Further bioactivity-guided fractionation resulted in the isolation of three PTP1 B inhibitory ursane-type triterpenes: ursolic acid(1), 2-oxopomolic acid(2), and 2α, 19α-dihydroxy-3-oxo-urs-12-en-28-oic acid(3). Kinetics analyses revealed that 1 was a non-competitive PTP1 B inhibitor, and 2 and 3 were mixed type PTP1 B inhibitors. Compounds 1-3 and structurally related triterpenes(4-8) were further analyzed the structure-activity relationship, and were evaluated the inhibitory selectivity against four homologous protein tyrosine phosphatases(TCPTP, VHR, SHP-1 and SHP-2). Molecular docking simulations were also carried out, and the result indicated that 1, 3-acetoxyurs-12-ene-28-oic acid(5), and pomolic acid-3β-acetate(6) bound at the allosteric site including α3, α6, and α7 helix of PTP1 B.

关键词： Protein tyrosine phosphatase 1B Raspberry Rubus chingii Triterpene Ursane

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Microcalorimetric Study on tyrosine Oxidation Catalyzed by Tyrosinase

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Chinese Chemical Letters 2003年第6期14卷 619-622页

作者： JunYAO YiLIU TianZhiWANG JianBenLIU PengLIU ZiNiuYU KeyLaboratoryofMicrobiologyofChineseAgriculturalMinistry HuazhongAgriculturalUniversityWuhan430070 CollegeofChemistryandMolecularScience WuhanUniversityWuhan430072 CollegeofLifeScienceandChemistry JishouUniversityJishou416000

Through the method of initial heat release rate, the kinetic property of tyrosine oxidation catalyzed by tyrosinase from Pseudomonas maltophilia was investigated using a LKB-2107 batch microcalorimeter. tyrosine was catalyzed and oxidized into L-dopa, then into melanin catalyzed by tyrosinase. We found that the tyrosinase reaction obeyed the Michaelis-Menten kinetics, and at 298.15K and pH 7.0, the initial exothermic rate (W0 ) are in the range of 0.1567~0.5704 mJ·s-1, the maximum exothermic rate (Wmax) are in 0.4152 ~ 0.8143mol·L-1, and mean value of the Michaelis constant (Km) is 2.199±0.105104 mol·L-1.

关键词： tyrosine tyrosinase-catalyzed oxidation reaction microcalorimetry thermokinetics.

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