Molecular architecture of leishmania EF-1alpha reveals a novel site that may modulate protein translation: a possible target for drug development.

Abstract:

:Elongation factor-1alpha plays an essential role in eukaryotic protein biosynthesis. Recently, we have shown by protein structure modeling the presence of a hairpin-loop of 12 amino acids in mammalian EF-1alpha that is absent in the leishmania homologue [D. Nandan, A. Cherkasov, R. Sabouti, T. Yi, N.E. Reiner, Molecular cloning, biochemical and structural analysis of elongation factor-1 alpha from Leishmania donovani: comparison with the mammalian homologue, Biochem. Biophys. Res. Commun. 302 (2003) 646-652]. As a consequence of this deletion, an exposed region is available on the main body of leishmania EF-1alpha. Here we report the generation of an anti-EF-1alpha antibody (DN-3) which bound selectively to the exposed region of leishmania EF-1alpha, with no reactivity with human EF-1alpha. In a leishmania cell-free protein translation system, DN-3 substantially inhibited protein translation. A similar inhibitory effect was observed when a specific peptide based on the exposed region was used in the cell-free protein translation assay. The application of structure-based in silico methods to identify potential ligands to target the exposed region identified a small molecule that selectively attenuated in vitro translation using leishmania extracts. Moreover, this small molecule showed selective suppressive effect on multiplication of leishmania in culture. Taken together, these findings identify a novel, exposed region in leishmania EF-1alpha that may be involved in protein synthesis and a potential site for drug targeting.

authors

Lopez M,Cherkasov A,Nandan D

doi

10.1016/j.bbrc.2007.03.077

subject

Has Abstract

pub_date

2007-05-18 00:00:00

pages

886-92

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(07)00530-X

journal_volume

356

pub_type

杂志文章
  • Identification of NDRG1-regulated genes associated with invasive potential in cervical and ovarian cancer cells.

    abstract::N-myc downstream regulated gene 1 (NDRG1) is an important gene regulating tumor invasion. In this study, shRNA technology was used to suppress NDRG1 expression in CaSki (a cervical cancer cell line) and HO-8910PM (an ovarian cancer cell line). In vitro assays showed that NDRG1 knockdown enhanced tumor cell adhesion, m...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2011.03.140

    authors: Zhao G,Chen J,Deng Y,Gao F,Zhu J,Feng Z,Lv X,Zhao Z

    更新日期:2011-04-29 00:00:00

  • AICAR induces AMPK-independent programmed necrosis in prostate cancer cells.

    abstract::AICAR (5-Aminoimidazole-4-carboxamide riboside or acadesine) is an AMP-activated protein kinase (AMPK) agonist, which induces cytotoxic effect to several cancer cells. Its potential activity in prostate cancer cells and the underlying signaling mechanisms have not been extensively studied. Here, we showed that AICAR p...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2016.04.077

    authors: Guo F,Liu SQ,Gao XH,Zhang LY

    更新日期:2016-05-27 00:00:00

  • GLP-1 receptor antagonist as a potential probe for pancreatic beta-cell imaging.

    abstract::We examined exendin(9-39), an antagonist of glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), as a potential probe for imaging of pancreatic beta-cells. To evaluate in vitro receptor specificity, binding assay was performed using dispersed mouse islet cells. Binding assay showed competitive inhibition of [(125)I]BH-e...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2009.09.014

    authors: Mukai E,Toyoda K,Kimura H,Kawashima H,Fujimoto H,Ueda M,Temma T,Hirao K,Nagakawa K,Saji H,Inagaki N

    更新日期:2009-11-20 00:00:00

  • Isolation and partial characterization of the gene for cytochrome P-450 3a (P-450ALC) and a second closely related gene.

    abstract::Two genes that hybridize to the cDNA for alcohol-inducible cytochrome P-450 form 3a (P-450ALC) have been isolated from a rabbit genomic library and characterized by restriction mapping, hybridization, and partial sequence analysis. The genes show extensive sequence similarity as judged by hybridization at high stringe...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/0006-291x(88)90479-2

    authors: Khani SC,Porter TD,Coon MJ

    更新日期:1988-01-15 00:00:00

  • BST-2 is a potential activator of invasion and migration in tamoxifen-resistant breast cancer cells.

    abstract::Bone marrow stromal cell antigen 2 (BST-2) is a type II transmembrane protein that is known to be a therapeutic target in several types of cancer. However, despite its clinical importance, the roles of BST-2 expression have remained elusive. Here, we found that BST-2 expression is up-regulated in tamoxifen-resistant M...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2013.05.043

    authors: Yi EH,Yoo H,Noh KH,Han S,Lee H,Lee JK,Won C,Kim BH,Kim MH,Cho CH,Ye SK

    更新日期:2013-06-14 00:00:00

  • Different conformational dynamics of β-arrestin1 and β-arrestin2 analyzed by hydrogen/deuterium exchange mass spectrometry.

    abstract::Arrestins have important roles in G protein-coupled receptor (GPCR) signaling including desensitization of GPCRs and G protein-independent signaling. There have been four arrestins identified: arrestin1, arrestin2 (e.g. β-arrestin1), arrestin3 (e.g. β-arrestin2), and arrestin4. β-Arrestin1 and β-arrestin2 are ubiquito...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2014.12.079

    authors: Yun Y,Kim DK,Seo MD,Kim KM,Chung KY

    更新日期:2015-01-30 00:00:00

  • Presence of centrin in the human parasite Giardia: a further indication of its ubiquity in eukaryotes.

    abstract::The presence and distribution of the cytoskeletal protein centrin in the lower eukaryote Giardia were determined using a monoclonal antibody to algal centrin. Immunofluorescence shows that centrin is a major component of rodlike structures associated with the flagella and strongly attached to the ventral disc and the ...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1006/bbrc.1995.2327

    authors: Belhadri A

    更新日期:1995-09-14 00:00:00

  • Expression of peroxisome proliferator activated receptor mRNA in normal and tumorigenic rodent mammary glands.

    abstract::The peroxisome proliferator activated receptors (PPARs) alpha, beta/delta, and gamma are novel nuclear hormone receptors activated by long chain fatty acids and synthetic ligands and which regulate lipid metabolism. Recent studies have detected PPARgamma mRNA in human mammary tumor cell lines. The current study examin...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1006/bbrc.1998.9858

    authors: Gimble JM,Pighetti GM,Lerner MR,Wu X,Lightfoot SA,Brackett DJ,Darcy K,Hollingsworth AB

    更新日期:1998-12-30 00:00:00

  • 1,25-Dihydroxycholecalciferol enhances butyrate-induced p21(Waf1/Cip1) expression.

    abstract::Butyrate, a short-chain fatty acid produced in the colon, as well as its prodrug tributyrin, reduce proliferation and increase differentiation of colon cancer cells. p21(Waf1/Cip1) and p27(Kip1) are negative regulators of cell cycle and are thought to have a key function in the differentiation of various cell lines. W...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1006/bbrc.2001.4756

    authors: Gaschott T,Wächtershäuser A,Steinhilber D,Stein J

    更新日期:2001-04-27 00:00:00

  • Genistein, a tyrosine kinase inhibitor, blocks the cell cycle progression but not Ca2+ influx induced by BAY K8644 in FRTL-5 cells.

    abstract::IGF-I, when added to TSH-primed FRTL-5 cells, induces a long lasting Ca2+ influx and then DNA synthesis. Ca2+ channel agonist, BAYK 8644, is capable to mimic these effects on cell proliferation. We studied the effect of genistein, a specific tyrosine kinase inhibitor, on BAY K8644- or IGF-I- induced cell cycle progres...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1006/bbrc.1993.1120

    authors: Takano T,Takada K,Tada H,Nishiyama S,Amino N

    更新日期:1993-02-15 00:00:00

  • Inhibition of wortmannin activities by amino compounds.

    abstract::Wortmannin caused normal and strong inhibition on catecholamine secretion from bovine adrenal chromaffin cells and in vitro phosphoinositide 3-kinase activity in NaCl-, Na isethionate-, choline Cl-, Na acetate-, and N-acetyl glycine-based media. However, brief preincubation of wortmannin with the media containing amin...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2004.09.200

    authors: Isosaki M

    更新日期:2004-11-26 00:00:00

  • The modulation of growth by HMBA in PKC overproducing HT29 colon cancer cells.

    abstract::To examine whether protein kinase C (PKC) plays a role in mediating growth inhibitory effects of hexamethylene bisacetamide (HMBA) we compared a control H29 colon cancer cell line to a derivative, HT29-PKC7, that overexpresses high levels of PKC beta 1. We found that although HMBA markedly inhibited the growth of the ...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/0006-291x(91)91262-b

    authors: Choi PM,Weinstein IB

    更新日期:1991-12-16 00:00:00

  • Expression of p40/Epstein-Barr virus nuclear antigen 1 binding protein 2.

    abstract::Nucleolar protein p40/EBP2 is a proliferation-associated antigen that interacts with Epstein-Barr virus nuclear antigen 1 (EBNA1) to maintain the Epstein-Barr virus (EBV) episomes. The yeast p40/EBP2 functions in the processing of 27S-A into 27S-B ribosomal RNA. The present study reports high evolutionary conservation...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1006/bbrc.2001.4780

    authors: Henning D,Valdez BC

    更新日期:2001-05-04 00:00:00

  • FAD oxidizes the ERO1-PDI electron transfer chain: the role of membrane integrity.

    abstract::The molecular steps of the electron transfer in the endoplasmic reticulum from the secreted proteins during their oxidation are relatively unknown. We present here that flavine adenine dinucleotide (FAD) is a powerful oxidizer of the oxidoreductase system, Ero1 and PDI, besides the proteins of rat liver microsomes and...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2005.10.027

    authors: Papp E,Nardai G,Mandl J,Bánhegyi G,Csermely P

    更新日期:2005-12-16 00:00:00

  • Macrophage and endothelial cell nitric oxide synthesis: cell-type selective inhibition by NG-aminoarginine, NG-nitroarginine and NG-methylarginine.

    abstract::Many cell types are known to synthesize nitric oxide (NO.) from L-arginine. There appear to be at least two forms of NO. synthase: an inducible, tetrahydrobiopterin- and flavin-dependent activity exemplified by the macrophage enzyme and a constitutive, Ca+(+)-dependent activity exemplified by the endothelial cell enzy...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/0006-291x(90)91245-n

    authors: Gross SS,Stuehr DJ,Aisaka K,Jaffe EA,Levi R,Griffith OW

    更新日期:1990-07-16 00:00:00

  • EphA7 modulates apical constriction of hindbrain neuroepithelium during neurulation in Xenopus.

    abstract::Eph receptor tyrosine kinases (RTKs) and their ephrin ligands play multiple roles in the developing nervous system, including cell segregation, axon guidance and synaptic plasticity. Here we report the expression and function of EphA7 in Xenopus hindbrain development. EphA7 is specifically expressed in the hindbrain t...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2016.09.138

    authors: Wang X,Sun J,Li C,Mao B

    更新日期:2016-10-28 00:00:00

  • Impaired adult hippocampal neurogenesis and its partial reversal by chronic treatment of fluoxetine in a mouse model of Angelman syndrome.

    abstract::Angelman syndrome (AS) is a neurodevelopmental disorder characterized by severe cognitive and motor deficits, caused by the loss of function of maternally inherited Ube3a. Ube3a-maternal deficient mice (AS model mice) recapitulate many essential features of AS, but how the deficiency of Ube3a lead to such behavioural ...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2015.07.103

    authors: Godavarthi SK,Dey P,Sharma A,Jana NR

    更新日期:2015-09-04 00:00:00

  • Inhibition of Sendai virus hemagglutinin neuraminidase by the fusion protein.

    abstract::The Sendai virus envelope contains two glycoproteins: the fusion (F) protein and the hemagglutinin-neuraminidase (HN). Inactivation of F causes the loss of fusogenic activity and an increase of the neuraminidase activity of HN. After inactivation of F, HN can be inhibited by fetuin or asialofetuin, as already observed...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1006/bbrc.1994.1799

    authors: Dallocchio F,Tomasi M,Bellini T

    更新日期:1994-06-15 00:00:00

  • Molecular cloning and characterization of rat lin-10.

    abstract::In Caenorhabditis elegans, the vulval induction is mediated by tyrosine kinase receptor/Ras signal transduction pathway composed of the lin-3, let-23, and let-60 products. In addition to these gene products, the lin-2, lin-7, and lin-10 products are also implicated in this pathway. Lin-2 encodes a MAGUK and lin-7 enco...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1006/bbrc.1998.8142

    authors: Ide N,Hirao K,Hata Y,Takeuchi M,Irie M,Yao I,Deguchi M,Toyoda A,Nishioka H,Mizoguchi A,Takai Y

    更新日期:1998-02-13 00:00:00

  • Regulation by heme of the synthesis of cytochrome C oxidase subunits V and VII in yeast.

    abstract::The effects of heme on the synthesis of subunits V and VII of cytochrome c oxidase were examined in the heme-deficient yeast mutant, GL1. In vitro translation and immunodetection with subunit-specific antisera indicated a 50% decrease in both proteins, with RNA obtained from hemeless cells. Unsupplemented, pulse-label...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/0006-291x(85)91102-7

    authors: Gollub EG,Dayan J

    更新日期:1985-05-16 00:00:00

  • Disulfide isoforms of recombinant glia maturation factor beta.

    abstract::Recombinant human glia maturation factor beta (r-hGMF-beta) is a single-chain polypeptide (141 amino acid residues) containing three cysteines, at positions 7, 86 and 95. Nascent r-hGMF-beta exists in the reduced state and has no biological activity. The protein can be activated through oxidative refolding by incubati...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/0006-291x(90)91209-b

    authors: Zaheer A,Lim R

    更新日期:1990-09-14 00:00:00

  • Flagellar basal body flg operon as a virulence determinant of Vibrio vulnificus.

    abstract::Vibrio vulnificus, a halophilic estuarine bacterium causing a rapidly progressing fatal septicemia, is highly cytotoxic to eukaryotic cells. To identify new virulence factors associated with cytotoxicity, we constructed a mariner-based transposon (Tn Himar1) library of the highly virulent clinical isolate MO6-24/O hav...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/s0006-291x(03)00613-2

    authors: Ran Kim Y,Haeng Rhee J

    更新日期:2003-05-02 00:00:00

  • Graphene coating on the surface of CoCrMo alloy enhances the adhesion and proliferation of bone marrow mesenchymal stem cells.

    abstract::The objective was to investigate whether a graphene coating could improve the surface bioactivity of a cobalt-chromium-molybdenum-based alloy (CoCrMo). Graphene was produced by chemical vapor deposition and transferred to the surface of the CoCrMo alloy using an improved wet transfer approach. The morphology of the sa...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2018.02.152

    authors: Zhang Q,Li K,Yan J,Wang Z,Wu Q,Bi L,Yang M,Han Y

    更新日期:2018-03-18 00:00:00

  • Vesicular nucleotide transporter is involved in ATP storage of secretory lysosomes in astrocytes.

    abstract::Recent studies have suggested that astrocytes release gliotransmitters (i.e., ATP, L-glutamate, D-serine, and peptide hormones) and participate actively in synaptic functioning. Although ATP release from astrocytes modulates the activity of neurons, the mechanisms regulating the ATP release from astrocytes and the sou...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2013.07.043

    authors: Oya M,Kitaguchi T,Yanagihara Y,Numano R,Kakeyama M,Ikematsu K,Tsuboi T

    更新日期:2013-08-16 00:00:00

  • Structural organization of the human selenium-dependent phospholipid hydroperoxide glutathione peroxidase gene (GPX4): chromosomal localization to 19p13.3.

    abstract::The primary structure of human selenium-dependent phospholipid hydroperoxide glutathione peroxidase (GPX4) was determined by genomic cloning. The gene structure of GPX4 spans only 2.8 kb and consists of 7 exons. The coding sequence resides on all 7 exons, and the mitochondrial leader sequence is contained entirely wit...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1006/bbrc.1998.9086

    authors: Kelner MJ,Montoya MA

    更新日期:1998-08-10 00:00:00

  • BAP1 regulates AMPK-mTOR signalling pathway through deubiquitinating and stabilizing tumour-suppressor LKB1.

    abstract::Liver kinase B1 (LKB1), a tumour suppressor, participates in many cellular processes, including cell survival, growth, apoptosis, transformation, and metabolism. Upon performing yeast two-hybrid screening, co-immunoprecipitation, and GST pull-down, we identified that BRCA1-associated protein 1 (BAP1), a deubiquitinase...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2020.05.223

    authors: Yang C,Ding H,Yang Y,Yang L,Yang Y,Fang M,Ren J,Hu R,Wang C,Geng W

    更新日期:2020-09-03 00:00:00

  • Sulfiredoxin-1 alleviates high glucose-induced podocyte injury though promoting Nrf2/ARE signaling via inactivation of GSK-3β.

    abstract::Hyperglycemia-induced podocyte injury plays a vital role in the development of diabetic nephropathy. Sulfiredoxin-1 (Srxn1) is emerging as a cytoprotective protein that protects from various insults in a wide range of cell types. However, whether Srxn1 is involved in regulating hyperglycemia-induced podocyte injury an...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2019.06.157

    authors: Shen Y,Chen S,Zhao Y

    更新日期:2019-09-03 00:00:00

  • Determination of genes involved in the early process of molar root development initiation in rat by modified subtractive hybridization.

    abstract::Rat molars and incisors have different root patterning mechanisms: the former form a multirooted pattern while the latter form a single-rooted analogue. But the genetic signals that control root patterning are poorly understood. In this study, to identify the special molecular signals which may lead to the molar root ...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2007.09.087

    authors: Xing X,Deng Z,Yang F,Watanabe S,Wen L,Jin Y

    更新日期:2007-11-30 00:00:00

  • Transcriptional regulation of human angiopoietin-2 by transcription factor Ets-1.

    abstract::Angiopoietin-2 (Ang-2) plays an important role in destabilizing vessels for angiogenesis, however its transcriptional regulation has not been determined. Here we isolated about 3.2kb of the 5' upstream of the human Ang-2 gene and further characterized the transcriptional regulation of Ang-2. We found 10 Ets binding si...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2004.02.019

    authors: Hasegawa Y,Abe M,Yamazaki T,Niizeki O,Shiiba K,Sasaki I,Sato Y

    更新日期:2004-03-26 00:00:00

  • Members of the histone deacetylase superfamily differ in substrate specificity towards small synthetic substrates.

    abstract::Histone deacetylases (HDACs) are important enzymes for the transcriptional regulation of gene expression in eukaryotic cells. Deacetylation of epsilon-acetyl-lysine residues within the N-terminal tail of core histones mediates changes in both histone-DNA and histone-non-histone protein interactions. However, surprisin...

    journal_title:Biochemical and biophysical research communications

    pub_type: 杂志文章

    doi:10.1016/j.bbrc.2004.09.155

    authors: Riester D,Wegener D,Hildmann C,Schwienhorst A

    更新日期:2004-11-19 00:00:00