Novel inhibitors of glutamyl-tRNA(Glu) reductase identified through cell-based screening of the heme/chlorophyll biosynthetic pathway.

Abstract:

:The metabolite 5-aminolevulinic acid (ALA) is an early committed intermediate in the biosynthetic pathway of heme and chlorophyll formation. In plants, 5-aminolevulinic acid is synthesized via a two-step pathway in which glutamyl-tRNA(Glu) is reduced by glutamyl-tRNA(Glu) reductase (GluTR) to glutamate 1-semialdehyde, followed by transformation to 5-aminolevulinic acid catalyzed by glutamate 1-semialdehyde aminotransferase. Using an Escherichia coli cell-based high-throughput assay to screen small molecule libraries, we identified several chemical classes that specifically inhibit heme/chlorophyll biosynthesis at this point by demonstrating that the observed cell growth inhibition is reversed by supplementing the medium with 5-aminolevulinic acid. These compounds were further tested in vitro for inhibition of the purified enzymes GluTR and glutamate 1-semialdehyde aminotransferase as confirmation of the specificity and site of action. Several promising compounds were identified from the high-throughput screen that inhibit GluTR with an I(0.5) of less than 10 microM. Our results demonstrate the efficacy of cell-based high-throughput screening for identifying inhibitors of 5-aminolevulinic acid biosynthesis, thus representing the first report of exogenous inhibitors of this enzyme.

journal_name

Arch Biochem Biophys

authors

Loida PJ,Thompson RL,Walker DM,CaJacob CA

doi

10.1006/abbi.1999.1505

subject

Has Abstract

pub_date

1999-12-15 00:00:00

pages

230-7

issue

2

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(99)91505-9

journal_volume

372

pub_type

杂志文章
  • Bacterial expression of functional membrane-bound thromboxane synthase having intact sequence and truncated N-terminal hydrophobic segment.

    abstract::A full-length cDNA for human placental thromboxane synthase and a shortened cDNA lacking the sequence corresponding to the N-terminal 2-29 amino acids were expressed in Escherichia coli using a pCW expression vector. Both intact and truncated recombinant enzyme were found in the membrane fraction and were catalyticall...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.1995.1427

    authors: Xia Z,Tai HH

    更新日期:1995-08-20 00:00:00

  • Characterization and partial amino acid sequence of human plasma glutathione peroxidase.

    abstract::Human plasma glutathione peroxidase was purified to homogeneity and partially sequenced. Overlapping peptide fragments from three endopeptidase digests permitted the determination of one sequence of 32 contiguous amino acids and one sequence of 23 contiguous amino acids. Five additional unique peptide sequences withou...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(91)90048-n

    authors: Esworthy RS,Chu FF,Paxton RJ,Akman S,Doroshow JH

    更新日期:1991-05-01 00:00:00

  • Expression, purification, and in vivo activity of atrial natriuretic factor prohormone produced in Escherichia coli.

    abstract::Atrial muscles of the heart are known to produce polypeptide hormones called atrial natriuretic factors (ANF) which have potent diuretic and hypotensive action. These hormones are synthesized as a larger protein precursor called pro atrial natriuretic factor or proANF which contains the biologically active ANF sequenc...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(89)90294-4

    authors: Gierse JK,Olins PO,Devine CS,Marlay JD,Obukowicz MG,Mortensen LH,McMahon EG,Blaine EH,Seetharam R

    更新日期:1989-06-01 00:00:00

  • Substrate specificity and kinetic mechanism of Escherichia coli ribulokinase.

    abstract::L-ribulokinase is unusual among kinases since it phosphorylates all four 2-ketopentoses with almost the same k(cat) values. The K(m)'s differ, however, being 0.14 mM for L- and 0.39 mM for d-ribulose and 3.4 mM for l- and 16 mM for d-xylulose. In addition, L-arabitol is phosphorylated at C-5 (K(m) 4 mM) and ribitol (a...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.2001.2613

    authors: Lee LV,Gerratana B,Cleland WW

    更新日期:2001-12-15 00:00:00

  • Characterization of tryptic hydrolysis of alpha-lactalbumin/saponin mixture and structural change of alpha-lactalbumin interacting with soybean saponin.

    abstract::Bovine milk alpha-lactalbumin (alpha-La) was mixed with soybean saponin, and the resulting mixture was hydrolyzed by trypsin. Saponin increased the tryptic-hydrolysis level of alpha-La only at relatively high phosphate buffer concentrations (> or = 0.05 M). T(1) experiments with acetylated soybean saponin demonstrated...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/j.abb.2005.01.001

    authors: Shimoyamada M,Okada Y,Watanabe K,Yamauchi R

    更新日期:2005-03-15 00:00:00

  • Bone effects of vitamin D - Discrepancies between in vivo and in vitro studies.

    abstract::Vitamin D was discovered as an anti-rachitic agent, but even at present, there is no direct evidence to support the concept that vitamin D directly stimulates osteoblastic bone formation and mineralization. It appears to be paradoxical, but vitamin D functions in the process of osteoclastic bone resorption. In 1952, C...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章,评审

    doi:10.1016/j.abb.2011.11.011

    authors: Suda T,Takahashi F,Takahashi N

    更新日期:2012-07-01 00:00:00

  • Different mechanisms of tert-butyl hydroperoxide-induced lethal injury in normal and tumor thymocytes.

    abstract::Normal thymocytes and thymoma cells have been exposed to the toxic action of tert-butyl hydroperoxide (t-BOOH) to study the mechanisms of oxidative lethal cell injury and the sensitivity of normal and tumor cells to an oxidative stress. From our data, we can suggest that: (a) In thymoma cells two mechanisms can operat...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.1994.1283

    authors: Bartoli GM,Piccioni E,Agostara G,Calviello G,Palozza P

    更新日期:1994-07-01 00:00:00

  • In vivo and in vitro incorporation of endogenous nucleotides by the energy-transducing ATPase of Streptococcus faecalis.

    abstract::The soluble ATPase isolated from Streptococcus faecalis membranes containing tightly bound endogenous nucleotides do not exchange in the presence of ATP and Mg+2 added during the purification of the enzyme. In this paper the stoichiometry of endogenous nucleotides in the soluble ATPase obtained from (a) growing cells,...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(84)90432-6

    authors: Zlotnick GW,Abrams A

    更新日期:1984-05-01 00:00:00

  • Epigenetic DNA modification N6-methyladenine inhibits DNA replication by Sulfolobus solfataricus Y-family DNA polymerase Dpo4.

    abstract::Dpo4 is a representative model of Y-family DNA polymerase and is therefore one of the most intensively studied DNA polymerase. 6 mA, an epigenetic marker, plays important roles in regulation of various biological processes. However, its effects on DNA replication by Dpo4 is completely unknown. Here, we found that 6 mA...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/j.abb.2019.108120

    authors: Du K,Zhang S,Chen W,Dai M,Xu Z,Liang T,Huang W,Ling Y,Zhang H

    更新日期:2019-10-30 00:00:00

  • Chaperonins: The hunt for the Group II mechanism.

    abstract::Chaperonins are multi-subunit complexes that enhance the efficiency of protein-folding reactions by capturing protein substrates in their central cavities. They occur in all prokaryotic and eukaryotic cell types and, alone amongst molecular chaperones, chaperonin knockouts are always lethal. Chaperonins come in two fo...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章,评审

    doi:10.1016/j.abb.2008.03.015

    authors: Bigotti MG,Clarke AR

    更新日期:2008-06-15 00:00:00

  • Two Chinese hamster ovary glycosylation mutants affected in the conversion of GDP-mannose to GDP-fucose.

    abstract::A biochemical basis for the pea and lentil lectin resistance of two Chinese hamster ovary (CHO) cell mutants, Lec13 and Lec13A, was investigated. Studies of the G glycopeptides of vesicular stomatitis virus grown in the mutants indicated that Lec13 cells essentially lack the ability to add fucose to complex carbohydra...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(86)90031-7

    authors: Ripka J,Adamany A,Stanley P

    更新日期:1986-09-01 00:00:00

  • Molecular determinants of Golgi retention in the Punta Toro virus G1 protein.

    abstract::The G1 glycoprotein of Punta Toro virus, a member of the bunyavirus family, accumulates in the Golgi complex when it is expressed from cloned cDNA. We previously reported that the information necessary for Golgi retention of the G1 protein is located within the transmembrane domain and a portion of the cytoplasmic dom...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.1996.0547

    authors: Matsuoka Y,Chen SY,Holland CE,Compans RW

    更新日期:1996-12-01 00:00:00

  • Stimulatory effect of basic fibroblast growth factor on induction of heat shock protein 27 in osteoblasts: role of protein kinase C.

    abstract::In a previous study we showed that basic fibroblast growth factor (bFGF) stimulates activation of protein kinase C through phosphoinositide hydrolysis by phospholipase C and phosphatidylcholine hydrolysis by phospholipase D in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether bFGF stimulate...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.2000.2290

    authors: Kozawa O,Niwa M,Matsuno H,Ishisaki A,Kato K,Uematsu T

    更新日期:2001-04-15 00:00:00

  • The how's and why's of protein folding intermediates.

    abstract::The nature and role of intermediates have been the subject of much heated debate in the field of protein folding. Historically, intermediates were viewed as essential stepping-stones that guide a protein through the folding process to the native state. However, with the experimental identification of numerous small pr...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章,评审

    doi:10.1016/j.abb.2012.10.006

    authors: Tsytlonok M,Itzhaki LS

    更新日期:2013-03-01 00:00:00

  • Regulation of steroidogenesis in rat Leydig cells in culture: effect of human chorionic gonadotropin and dibutyryl cyclic AMP on the synthesis of cholesterol side chain cleavage cytochrome P-450 and adrenodoxin.

    abstract::Rat Leydig cells in primary culture were used as a model system to investigate the effects of human chorionic gonadotropin (hCG) and dibutyryl cyclic AMP (Bt2cAMP) on the synthesis of cholesterol side chain cleavage cytochrome P-450 (cytochrome P-450scc) and the iron-sulfur protein, adrenodoxin. Leydig cells isolated ...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(85)90178-x

    authors: Anderson CM,Mendelson CR

    更新日期:1985-05-01 00:00:00

  • 1,25-Dihydroxyvitamin D₃ suppresses inflammation-induced expression of plasminogen activator inhibitor-1 by blocking nuclear factor-κB activation.

    abstract::Plasminogen activator inhibitor (PAI)-1 is a major fibrinolytic inhibitor. High PAI-1 is associated with increased renal and cardiovascular disease risk. Previous studies demonstrated PAI-1 down-regulation by 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), but the molecular mechanism remains unknown. Here we show that exposur...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/j.abb.2010.12.020

    authors: Chen Y,Kong J,Sun T,Li G,Szeto FL,Liu W,Deb DK,Wang Y,Zhao Q,Thadhani R,Li YC

    更新日期:2011-03-15 00:00:00

  • Human erythrocyte pyrimidine 5'-nucleotidase, PN-I.

    abstract::Erythrocyte maturation is accompanied by RNA degradation and release of mononucleotides. Pyrimidine 5'-nucleotidase, PN-I, has been purified and characterized. The molecular and enzymatic properties determined for the enzyme shows a 36-kDa and 5.1 pI monomeric protein with no disulfide bridges and no phosphate content...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.2001.2676

    authors: Amici A,Magni G

    更新日期:2002-01-15 00:00:00

  • Oviduct dolichyl phosphate phosphatase: estrogen effects and a possible biosynthetic role.

    abstract::Estrogen-induced chick oviduct differentiation is accompanied by an increased capacity for protein glycosylation. A portion of this increase has been attributed to increased levels of dolichyl phosphate (Dol-P). Hormone withdrawal leads to an apparent decrease in Dol-P. Dol-P metabolism in the oviduct has been studied...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(84)90301-1

    authors: DeRosa PA,Lucas JJ

    更新日期:1984-11-01 00:00:00

  • 3,5,3'-triiodothyronine induces mitochondrial permeability transition mediated by reactive oxygen species and membrane protein thiol oxidation.

    abstract::Ca(2+)-loaded rat liver mitochondria treated with 3,5,3'-triiodothyronine (T3) undergo nonspecific inner membrane permeabilization, as evidenced by mitochondrial swelling, a decrease in membrane potential (delta psi), and an increase in the rate of oxygen uptake. T3 analogues thyroxine (T4), 3',5'-diiodothyronine (T2)...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.1998.0657

    authors: Castilho RF,Kowaltowski AJ,Vercesi AE

    更新日期:1998-06-01 00:00:00

  • Low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor on murine peritoneal macrophages mediates the binding and catabolism of low-density lipoprotein.

    abstract::Low-density lipoprotein receptor-related protein (LRP)/alpha 2-macroglobulin receptor is a member of the low-density lipoprotein receptor family. It is known to bind a wide variety of unrelated ligands including alpha 2-macroglobulin-proteinase complexes, tissue plasminogen activator, apolipoprotein E-enriched very lo...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.1996.0044

    authors: Wu SM,Pizzo SV

    更新日期:1996-02-01 00:00:00

  • Oxidation mechanism of vitamin E analogue (Trolox C, 6-hydroxy-2,2,5,7,8-pentamethylchroman) and vitamin E by horseradish peroxidase and myoglobin.

    abstract::The oxidation of 6-hydroxy-2,2,5,7,8-pentamethylchroman, Trolox C, and alpha-tocopherol by horseradish peroxidase was examined by stopped-flow and ESR experiments. The catalytic intermediate of horseradish peroxidase during the oxidation of vitamin E analogues and vitamin E was invariably Compound II, and rate constan...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(92)90280-a

    authors: Nakamura M,Hayashi T

    更新日期:1992-12-01 00:00:00

  • Metabolic impact of overexpression of liver glycogen synthase with serine-to-alanine substitutions in rat primary hepatocytes.

    abstract::To investigate the effect of elevation of liver glycogen synthase (GYS2) activity on glucose and glycogen metabolism, we performed adenoviral overexpression of the mutant GYS2 with six serine-to-alanine substitutions in rat primary hepatocytes. Cell-free assays demonstrated that the serine-to-alanine substitutions cau...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/j.abb.2007.08.006

    authors: Kadotani A,Fujimura M,Nakamura T,Ohyama S,Harada N,Maruki H,Tamai Y,Kanatani A,Eiki J,Nagata Y

    更新日期:2007-10-15 00:00:00

  • Evidence for unusual stability of ADP-ribosyl linkage to membrane proteins of a murine leukemic cell line.

    abstract::A set of membrane proteins from murine myelomonocytic leukemia cell line WEHI-3BD+ was found to be ADP-ribosylated. Both this ADP-ribosylation reaction and granulocytic differentiation in response to recombinant G-CSF were inhibited approximately 50% by 2 mM benzamide, suggesting a correlation between these two proces...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.1993.1198

    authors: Hanson K,Aboul-Ela N,Jacobson MK,Wu MC

    更新日期:1993-04-01 00:00:00

  • Antibacterial properties and mechanism of graphene oxide-silver nanocomposites as bactericidal agents for water disinfection.

    abstract::Providing clean and affordable drinking water without harmful disinfection byproducts generated by conventional chemical disinfectants gives rise to the need for technological innovation. Nanotechnology has great potential in purifying water and wastewater treatment. A graphene oxide-silver (GO-Ag) nanocomposite with ...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/j.abb.2016.04.018

    authors: Song B,Zhang C,Zeng G,Gong J,Chang Y,Jiang Y

    更新日期:2016-08-15 00:00:00

  • Oxidative metabolism in rat hepatocytes and mitochondria during sepsis.

    abstract::We hypothesized that cellular oxygen consumption is abnormal during sepsis as a result of increased oxidative stress and selective mitochondrial damage. In a rat model of sepsis (cecal ligation and puncture), we studied the respiratory characteristics of isolated hepatocytes and liver mitochondria 16 h after onset of ...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.1997.0264

    authors: Kantrow SP,Taylor DE,Carraway MS,Piantadosi CA

    更新日期:1997-09-15 00:00:00

  • (6R)-5,6,7,8-tetrahydro-L-biopterin modulates nitric oxide-associated soluble guanylate cyclase activity in the rat cerebellum.

    abstract::(6R)-5,6,7,8-Tetrahydro-L-biopterin (R-THBP) is a cofactor not only for aromatic amino acid hydroxylases in mammalian tissues but also for nitric oxide synthase (NOS) induced by endotoxins or cytokines in some kinds of cells. Recently it has been reported that nitric oxide (NO) has biological activity in endothelium a...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(92)90472-9

    authors: Nunokawa Y,Ishihara T,Kanai T,Noguchi T

    更新日期:1992-11-01 00:00:00

  • Catalytic oxidation of acetaminophen by tyrosinase in the presence of L-proline: a kinetic study.

    abstract::A kinetic study of acetaminophen oxidation by tyrosinase in the presence of a physiological nucleophilic agent such as the amino acid L-proline is performed in the present paper. The o-quinone product of the catalytic activity, 4-acetamido-o-benzoquinone, becomes unstable through the chemical addition of L-proline, in...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/s0003-9861(03)00288-1

    authors: Valero E,Varón R,García-Carmona F

    更新日期:2003-08-15 00:00:00

  • Biochemical and functional interactions between HIV-1 Tat protein and TAR RNA.

    abstract::HIV-1 trans-activator of transcription (Tat) is an unusual transcriptional activator in being an RNA-binding protein rather than a DNA-binding protein. Recent findings have greatly advanced our understanding of the transcriptional function(s) of this protein. Here we review how Tat interacts with trans-activation resp...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章,评审

    doi:10.1006/abbi.1999.1206

    authors: Rana TM,Jeang KT

    更新日期:1999-05-15 00:00:00

  • Communications between bone cells and hematopoietic stem cells.

    abstract::The skeletal system, while characterized by a hard tissue component, is in fact an extraordinarily dynamic system, with disparate functions ranging from structural support, movement and locomotion and soft-organ protection, to the maintenance of calcium homeostasis. Amongst these functions, it has long been known that...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章,评审

    doi:10.1016/j.abb.2008.04.001

    authors: Porter RL,Calvi LM

    更新日期:2008-05-15 00:00:00

  • Phospholipid modulation of low-Km cyclic AMP phosphodiesterase activity on rat adipocyte microsomes.

    abstract::The ability of nine phospholipids to alter the activity of low-Km cyclic AMP phosphodiesterase was examined in microsomal fractions of rat adipocytes. The enzyme was activated by phosphatidylserine (21% at 300 microM) and phosphatidylglycerol (36% at 300 microM). The activation was concentration dependent over the ran...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(83)90015-2

    authors: Macaulay SL,Kiechle FL,Jarett L

    更新日期:1983-08-01 00:00:00