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Rohit Shrivastava Nitin Tupperwar Bar Schwartz Nofar Baron Michal Shapira 《International journal of molecular sciences》2021,22(8)
Leishmania parasites cycle between sand fly vectors and mammalian hosts, transforming from extracellular promastigotes that reside in the vectors’ alimentary canal to obligatory intracellular non-motile amastigotes that are harbored by macrophages of the mammalian hosts. The transition between vector and host exposes them to a broad range of environmental conditions that induces a developmental program of gene expression, with translation regulation playing a key role. The Leishmania genome encodes six paralogs of the cap-binding protein eIF4E. All six isoforms show a relatively low degree of conservation with eIF4Es of other eukaryotes, as well as among themselves. This variability could suggest that they have been assigned discrete roles that could contribute to their survival under the changing environmental conditions. Here, we describe LeishIF4E-5, a LeishIF4E paralog. Despite the low sequence conservation observed between LeishIF4E-5 and other LeishIF4Es, the three aromatic residues in its cap-binding pocket are conserved, in accordance with its cap-binding activity. However, the cap-binding activity of LeishIF4E-5 is restricted to the promastigote life form and not observed in amastigotes. The overexpression of LeishIF4E-5 shows a decline in cell proliferation and an overall reduction in global translation. Immuno-cytochemical analysis shows that LeishIF4E-5 is localized in the cytoplasm, with a non-uniform distribution. Mass spectrometry analysis of proteins that co-purify with LeishIF4E-5 highlighted proteins involved in RNA metabolism, along with two LeishIF4G paralogs, LeishIF4G-1 and LeishIF4G-2. These vary in their conserved eIF4E binding motif, possibly suggesting that they can form different complexes. 相似文献
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Emma Martínez-Alonso Natalia Guerra-Prez Alejandro Escobar-Peso Lorena Peracho Rocío Vera-Lechuga Antonio Cruz-Culebras Jaime Masjuan Alberto Alczar 《International journal of molecular sciences》2022,23(3)
Ischemic strokes are caused by a reduction in cerebral blood flow and both the ischemic period and subsequent reperfusion induce brain injury, with different tissue damage depending on the severity of the ischemic insult, its duration, and the particular areas of the brain affected. In those areas vulnerable to cerebral ischemia, the inhibition of protein translation is an essential process of the cellular response leading to delayed neuronal death. In particular, translation initiation is rate-limiting for protein synthesis and the eukaryotic initiation factor (eIF) 4F complex is indispensable for cap-dependent protein translation. In the eIF4F complex, eIF4G is a scaffolding protein that provides docking sites for the assembly of eIF4A and eIF4E, binding to the cap structure of the mRNA and stabilizing all proteins of the complex. The eIF4F complex constituents, eIF4A, eIF4E, and eIF4G, participate in translation regulation by their phosphorylation at specific sites under cellular stress conditions, modulating the activity of the cap-binding complex and protein translation. This work investigates the phosphorylation of eIF4G1 involved in the eIF4E/eIF4G1 association complex, and their regulation in ischemia-reperfusion (IR) as a stress-inducing condition. IR was induced in an animal model of transient cerebral ischemia and the results were studied in the resistant cortical region and in the vulnerable hippocampal CA1 region. The presented data demonstrate the phosphorylation of eIF4G1 at Ser1147, Ser1185, and Ser1231 in both brain regions and in control and ischemic conditions, being the phosphorylation of eIF4G1 at Ser1147 the only one found in the eIF4E/eIF4G association complex from the cap-containing matrix (m7GTP-Sepharose). In addition, our work reveals the specific modulation of the phosphorylation of eIF4G1 at Ser1147 in the vulnerable region, with increased levels and colocalization with eIF4E in response to IR. These findings contribute to elucidate the molecular mechanism of protein translation regulation that underlies in the balance of cell survival/death during pathophysiological stress, such as cerebral ischemia. 相似文献
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3‐Substituted Indazoles as Configurationally Locked 4EGI‐1 Mimetics and Inhibitors of the eIF4E/eIF4G Interaction 下载免费PDF全文
Dr. Revital Yefidoff‐Freedman Dr. Ting Chen Dr. Rupam Sahoo Dr. Limo Chen Prof. Gerhard Wagner Prof. Dr. Jose A. Halperin Prof. Bertal H. Aktas Prof. Michael Chorev 《Chembiochem : a European journal of chemical biology》2014,15(4):595-611
4EGI‐1, the prototypic inhibitor of eIF4E/eIF4G interaction, was identified in a high‐throughput screening of small‐molecule libraries with the aid of a fluorescence polarization assay that measures inhibition of binding of an eIF4G‐derived peptide to recombinant eIF4E. As such, the molecular probe 4EGI‐1 has potential for the study of molecular mechanisms involved in human disorders characterized by loss of physiological restraints on translation initiation. A hit‐to‐lead optimization campaign was carried out to overcome the configurational instability in 4EGI‐1, which stems from the E‐to‐Z isomerization of the hydrazone function. We identified compound 1 a , in which the labile hydrazone was incorporated into a rigid indazole scaffold, as a promising rigidified 4EGI‐1 mimetic lead. In a structure–activity relationship study directed towards probing the structural latitude of this new chemotype as an inhibitor of eIF4E/eIF4G interaction and translation initiation we identified 1 d , an indazole‐based 4EGI‐1 mimetic, as a new and improved lead inhibitor of eIF4E/eIF4G interaction and a promising molecular probe candidate for elucidation of the role of cap‐dependent translation initiation in a host of pathophysiological states. 相似文献
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根据Kornblum反应,采用二甲基亚砜(DMSO)氧化E-1-乙酰氧基-4-氯-3-甲基-2-丁烯(ACMB)合成E-4-乙酰氧基-2-甲基-2-丁烯-1-醛(AMBA)。在实验过程中,采用气相色谱跟踪,研究了反应时问、反应温度和催化剂用量等因素对主副产物收率的影响并确定了较佳反应条件;反应时间24h,反应温度80℃,原料缓慢滴加,KH2PO4:K2HPO4:ACMB=0.14:1.27:1(摩尔比),催化剂用量与原料ACMB比为0.12:1(摩尔比)。同时,对从未报道过的副产物E-1-乙酰氧基-4-甲巯基-3-甲基-2-丁烯(AMMB)进行了结构鉴定,并推测了其形成机理。 相似文献
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2, 4, 6-三硝基氯苯的表征及晶体结构 总被引:2,自引:0,他引:2
从丙酮溶液中培养了2,4,6-三硝基氯苯(TNCB)的单晶,通过元素分析、红外光谱分析和X-射线单晶衍射分析对TNCB进行了结构表征,属于单斜晶系,P2(1)/c空间群,a=1.2501(1)
nm, b= 0.6803(1) nm, c=1.1038(1) nm, β= 102.842(9)°, V= 0.91526(15) nm3, Z=2, Dc = 1.797
g/cm3, μ(MoKα)=0.438 /mm, F(000)=496, R1= 0.0395, ωR2= 0.0991. 相似文献
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采用电絮凝气浮法处理分散艳蓝E-4R染料废水,考察了电解时间、废水初始浓度、pH值及外加电解质氯化钠和絮凝剂等不同反应条件对废水处理效果的影响。结果表明,染料废水脱色率随着电解时间的加大而逐渐增大并随初始浓度的增大而慢慢降低;pH值在2.5~10范围内电解均可获得较高的脱色率。初始浓度为400 mg/L的染料废水,电解20 min后脱色率即达87.39%,但TOC去除率只有10.49%。投加50 mg/L氯化钠后,脱色率和TOC去除率分别达到93.61%和73.49%,TOC去除率提高60%以上。在电解的条件下投加不同絮凝剂能提高染料废水的处理效果,其处理效果从大到小依次为:硫酸铝>三氯化铝>硫酸亚铁,它们的适宜用量分别为50,100,100 mg/L。 相似文献
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在浓盐酸中由环己酮和2,6-二甲基苯胶一步合成了多取代基的4,4'-二胺基-2,2',6,6'-四甲基二苯基环己烷。报道了该二胺的纯化,井使用元素分析、红外光谱、核磁共振谱等分析手段对其进行了表征。 相似文献
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A novel adsorbent, amino-alky cellulose (AmAC), is prepared by chlorination and amination of hydroxyethyl cellulose (HEC). AmAC are characterized by 13C-NMR and used as adsorbent to remove 2, 4, 6-trinitrotoluene (TNT) from waste water. Effects of various parameters including solvent and amine group content are studied. Adsorption mechanisms are also analyzed. Results show that the maximum adsorption capacity is 69.23 mg g?1 and removal efficiency of 99.30%, while the adsorption deeds are attributed to the hydrogen bond between TNT molecules and amino-alky cellulose. The equilibrium sorption is well demonstrated by Freundlich isotherm model. The reusability experiment shows the adsorbed TNT could be desorbed by ethanol eluant when the pH is 1. 相似文献
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以SO42-/ZrO2为催化剂,在无溶剂条件下,丙醛与丙二酸发生Knoevenagel缩合反应合成了E-2-戊烯酸。结果表明,SO42-/ZrO2对丙醛与丙二酸的Knoevenagel反应具有很高的催化活性,n(丙二酸)/n(丙醛)=1.2,催化剂用量为10%(相对于丙醛的质量),回流反应3 h,E-2-戊烯酸的产率为83.5%,纯度98.2%。催化剂可以重复使用多次。 相似文献
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以丙腈为原料,与氯化氢、氨气反应合成丙眯盐酸盐,在水溶液中同乙酰乙酸乙酯反应合成4-甲基-2-乙基-6-羟基嘧啶。考察了反应时间、反应温度、物料配比、pH值对4-甲基-2-乙基-6-羟基嘧啶收率的影响。优化条件为:反应温度40℃、反应的pH=12.4、反应时间为6~7h、乙酰乙酸乙酯与丙腈的物质的量比为1.09:1.0,在此条件下反应的总收率为88.7%。 相似文献