The dihydroorotate dehydrogenases: Past and present.

Abstract:

:The flavoenzyme dihydroorotate dehydrogenase catalyzes the stereoselective oxidation of (S)-dihydroorotate to orotate in the fourth of the six conserved enzymatic reactions involved in the de novo pyrimidine biosynthetic pathway. Inhibition of pyrimidine metabolism by selectively targeting DHODHs has been exploited in the development of new therapies against cancer, immunological disorders, bacterial and viral infections, and parasitic diseases. Through a chronological narrative, this review summarizes the efforts of the scientific community to achieve our current understanding of structural and biochemical properties of DHODHs. It also attempts to describe the latest advances in medicinal chemistry for therapeutic development based on the selective inhibition of DHODH, including an overview of the experimental techniques used for ligand screening during the process of drug discovery.

journal_name

Arch Biochem Biophys

authors

Reis RAG,Calil FA,Feliciano PR,Pinheiro MP,Nonato MC

doi

10.1016/j.abb.2017.06.019

subject

Has Abstract

pub_date

2017-10-15 00:00:00

pages

175-191

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(17)30272-2

journal_volume

632

pub_type

杂志文章,评审
  • The fate of the carboxyl oxygens during D-proline reduction by clostridial proline reductase.

    abstract::D-Proline is converted to 5-amino valeric acid by D-proline reductase. This conversion involves the reductive cleavage of the alpha-carbon-nitrogen bond. We have examined the fate of the carboxyl oxygen atoms during conversion of D-proline to delta-NH2-valeric acid. 18O atoms from the carboxyl group of D-proline are n...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.1994.1262

    authors: Arkowitz RA,Dhe-Paganon S,Abeles RH

    更新日期:1994-06-01 00:00:00

  • Triplex forming ability of a c-myc promoter element predicts promoter strength.

    abstract::Most transcription factors are believed to bind promoter elements in the B-DNA conformation, wherein linear sequence determines specificity. However, there are promoter elements that can form complex structures such as intramolecular triplexes, and these structures may participate in the activity of these promoter ele...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.1994.1162

    authors: Firulli AB,Maibenco DC,Kinniburgh AJ

    更新日期:1994-04-01 00:00:00

  • Direct proof that phorbol ester accelerates the use of choline phosphate for phosphatidylcholine synthesis in intact cells.

    abstract::Phorbol 12-myristate 13-acetate (PMA), a potent activator of protein kinase C, stimulates both the cellular uptake of radiolabeled choline and the activity of CTP:phosphocholine cytidylyltransferase resulting in increased incorporation of choline into phosphatidylcholine (PtdCho). Because of these multiple actions, it...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.1996.0497

    authors: Kiss Z

    更新日期:1996-11-01 00:00:00

  • Brief history of glyoxalase I and what we have learned about metal ion-dependent, enzyme-catalyzed isomerizations.

    abstract::Glyoxalase I, a member of the metalloglutathione (GSH) transferase superfamily, plays a critical detoxification role in cells by catalyzing the conversion of cytotoxic methylglyoxal (as the diastereomeric GSH-thiohemiacetals) to S-D-lactoylglutathione via a 1,2-hydrogen transfer. The mechanism-of-action of this Zn2+-m...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章,评审

    doi:10.1006/abbi.2000.2253

    authors: Creighton DJ,Hamilton DS

    更新日期:2001-03-01 00:00:00

  • Epitope mapping of rat cytochrome P450 2B1 using glutathione S-transferase-2B1 fusion constructs.

    abstract::We have previously produced 12 monoclonal antibodies (MAbs) against rat cytochrome P450(CYP)2B1, and 8 of these inhibit CYP2B1 catalytic activity to varying extents. Using competitive binding studies we showed that this collection of 12 MAbs recognize at least 6 spatially distinct epitopes. The complete coding sequenc...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.2000.1922

    authors: Parimoo B,Thomas PE

    更新日期:2000-08-01 00:00:00

  • Purification, characterization, and subcellular localization of an acid phosphatase from black mustard cell-suspension cultures: comparison with phosphoenolpyruvate phosphatase.

    abstract::An acid phosphatase from Brassica nigra (black mustard) leaf petiole cell-suspension cultures has been purified 1633-fold to a final specific activity of 1225 (mumols orthophosphate produced/min)/mg protein and near homogeneity. The native protein was a glycosylated monomer having a molecular mass of 60 kDa and a pI o...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(91)90033-f

    authors: Duff SM,Lefebvre DD,Plaxton WC

    更新日期:1991-04-01 00:00:00

  • Thioredoxin peroxidase-1 (peroxiredoxin-1) is increased in thioredoxin-1 transfected cells and results in enhanced protection against apoptosis caused by hydrogen peroxide but not by other agents including dexamethasone, etoposide, and doxorubicin.

    abstract::Thioredoxin-1 (Trx-1) is a small redox oncoprotein whose expression is increased in a number of human primary cancers where it is associated with aggressive tumor growth, inhibition of apoptosis and decreased patient survival. We report that Trx-1-transfected MCF-7 human breast cancer cells have increased expression o...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.2001.2435

    authors: Berggren MI,Husbeck B,Samulitis B,Baker AF,Gallegos A,Powis G

    更新日期:2001-08-01 00:00:00

  • Substrate inhibition of Pseudomonas aeruginosa elastase by 3-(2-furyl)acryloyl-glycyl-L-phenylalanyl-L-phenylalanine.

    abstract::The kinetics of hydrolysis by Pseudomonas aeruginosa elastase at 37 degrees C and pH 7.3 of 3-(2-furyl)acryloyl-glycyl-L-phenylalanyl-L-phenylalanine is compatible with nonproductive substrate inhibition, i.e., v = V.[S]/(Km + [S] + [S]2/K1), and the values of Km, Ki, and kappa cat are 1.4 mM, 5.0 mM, and 240 s-1, res...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(88)90283-4

    authors: Poncz L

    更新日期:1988-11-01 00:00:00

  • Applications of NMR to structure determination of RNAs large and small.

    abstract::Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool to investigate the structure and dynamics of RNA, because many biologically important RNAs have conformationally flexible structures, which makes them difficult to crystallize. Functional, independently folded RNA domains, range in size between simple st...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章,评审

    doi:10.1016/j.abb.2017.06.003

    authors: Barnwal RP,Yang F,Varani G

    更新日期:2017-08-15 00:00:00

  • IgG-Fc glycoengineering in non-mammalian expression hosts.

    abstract::The remarkable success of therapeutic applications of immunoglobulin G (IgG) in form of monoclonal antibodies and pooled immunoglobulin G preparations has directed attention to this class of glycoproteins. It is commonly appreciated that oligosaccharides attached to the Fc-region play a critical role in the biological...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章,评审

    doi:10.1016/j.abb.2012.05.011

    authors: Loos A,Steinkellner H

    更新日期:2012-10-15 00:00:00

  • Characteristics, substrate analysis, and intracellular location of Saccharomyces cerevisiae UMP kinase.

    abstract::The yeast Saccharomyces cerevisiae SOC8 DNA fragment was isolated as a wildtype dominant suppressor of the cdc8 mutation. The SOC8 has previously been proved to be allelic with URA6, encoding the UMP kinase in yeast cells. The protein has been purified to homogeneity. In this report, we describe the characteristics of...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.1993.1339

    authors: Jong A,Yeh Y,Ma JJ

    更新日期:1993-07-01 00:00:00

  • Conformational changes in plastocyanin.

    abstract::The visible and near-uv absorption and circular dichroic spectra were determined for spinach and poplar plastocyanin under a variety of conditions. The visible spectra showed that the copper center was invariant to changes in species, chemical modification with ethylenediamine, and addition of high concentrations of s...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(85)90259-0

    authors: Draheim JE,Anderson GP,Pan RL,Rellick LM,Duane JW,Gross EL

    更新日期:1985-02-15 00:00:00

  • The membrane potential modulates thrombin-stimulated Ca²⁺ mobilization and platelet aggregation.

    abstract::G protein-coupled receptors can be directly modulated by changes in transmembrane voltage in a variety of cell types. Here we show that, while changes in the membrane voltage itself do not induce detectable modifications in the cytosolic Ca(2+) concentration, platelet stimulation with thrombin or the PAR-1 and PAR-4 a...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/j.abb.2013.08.007

    authors: Albarrán L,Dionisio N,López E,Salido GM,Rosado JA

    更新日期:2013-10-15 00:00:00

  • Properties of the proteasome activator subunit PA28 alpha and its des-tyrosyl analog.

    abstract::The proteasome activator protein PA28 or 11 S regulator may play an important role in facilitating the generation of peptides for presentation by the MHC class I system. PA28 is composed of two homologous subunits termed alpha and beta. Removal of the carboxyl terminal tyrosine of the alpha subunit of PA28 abolishes a...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.1998.0918

    authors: Wilk S,Chen WE,Magnusson RP

    更新日期:1998-11-15 00:00:00

  • Effect of quercetin on cell protection via erythropoietin and cell injury of HepG2 cells.

    abstract::Quercetin is a flavonoid that has roles in both cytoprotection and cytotoxicity. The relation of queretin's cytoprotective and cytotoxic effects are unknown. Quercetin has been shown to induce expression of hypoxia-inducible factor, a protein that is known to regulate transcription of the erythropoietin (EPO) gene, an...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/j.abb.2017.10.013

    authors: Nishimura K,Matsumoto R,Yonezawa Y,Nakagawa H

    更新日期:2017-12-15 00:00:00

  • Metabolism of cyanide by Phanerochaete chrysosporium.

    abstract::The oxidation of veratryl alcohol (3,4-dimethoxybenzyl alcohol) by lignin peroxidase H2 (LiP H2) from the white rot fungus Phanerochaete chrysosporium was strongly inhibited by sodium cyanide. The I50 was estimated to be about 2-3 microM. In contrast, sodium cyanide binds to the native enzyme with an apparent sodium c...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(91)90604-h

    authors: Shah MM,Grover TA,Aust SD

    更新日期:1991-10-01 00:00:00

  • Multiple thioredoxin-mediated routes to detoxify hydroperoxides in Mycobacterium tuberculosis.

    abstract::Drug resistance and virulence of Mycobacterium tuberculosis are in part related to the pathogen's antioxidant defense systems. KatG(-) strains are resistant to the first line tuberculostatic isoniazid but need to compensate their catalase deficiency by alternative peroxidase systems to stay virulent. So far, only NADH...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/j.abb.2003.11.021

    authors: Jaeger T,Budde H,Flohé L,Menge U,Singh M,Trujillo M,Radi R

    更新日期:2004-03-01 00:00:00

  • Inhibition of cathepsin B and papain by peptidyl alpha-keto esters, alpha-keto amides, alpha-diketones, and alpha-keto acids.

    abstract::A series of peptidyl alpha-keto esters, alpha-keto amides, alpha-keto acids, and alpha-diketones were synthesized which reversibly inhibit papain and cathepsin B. Methyl 3-(N-benzyloxycarbonyl-L-phenylalanyl)amino-2-oxopropionate (a dicarbonyl compound) inhibits papain with a Ki value of 1 microM, whereas the Ki of 3-...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(90)90443-3

    authors: Hu LY,Abeles RH

    更新日期:1990-09-01 00:00:00

  • A role for His-160 in peroxide inhibition of S. cerevisiae S-formylglutathione hydrolase: evidence for an oxidation sensitive motif.

    abstract::While the general catalytic mechanism of the widespread serine hydrolase superfamily has been documented extensively, much less is known about its varied modes of functional modulation within biological systems. Under oxidizing conditions, inhibition of Saccharomyces cerevisiae S-formylglutathione hydrolase (SFGH, hom...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/j.abb.2012.08.001

    authors: Legler PM,Leary DH,Hervey WJ 4th,Millard CB

    更新日期:2012-12-01 00:00:00

  • Effect of orally administered secondary autoxidation products of linoleic acid on carbohydrate metabolism in rat liver.

    abstract::The effects of orally administered secondary autoxidation products of linoleic acid in rat liver were investigated. Their administration led to two toxic effects on hepatic carbohydrate metabolism, as compared to the administration of saline or linoleic acid used as controls. One effect was depletion of glucose 6-phos...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(87)90476-0

    authors: Ashida H,Kanazawa K,Minamoto S,Danno G,Natake M

    更新日期:1987-11-15 00:00:00

  • Massive production of farnesol-derived dicarboxylic acids in mice treated with the squalene synthase inhibitor zaragozic acid A.

    abstract::The zaragozic acids are potent inhibitors of squalene synthase. In vivo studies in mice confirmed our earlier observations that inhibition of squalene synthase by zaragozic acid A was accompanied by an increase in the incorporation of label from [3H]mevalonate into farnesyl-diphosphate (FPP)-derived isoprenoic acids (...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.1998.0704

    authors: Vaidya S,Bostedor R,Kurtz MM,Bergstrom JD,Bansal VS

    更新日期:1998-07-01 00:00:00

  • The effects of fur on the transcriptional and post-transcriptional regulation of MnSOD gene (sodA) in Escherichia coli.

    abstract::Earlier studies have shown that the Fur (ferric uptake regulation) protein acts as an anaerobic/aerobic repressor of MnSOD (sodA) expression. We found that the aerobic expression of sodA::lacZ fusion in a Fur- background to be threefold higher than in a Fur+ background. This effect of fur mutation was not seen in a st...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.1994.1115

    authors: Schrum LW,Hassan HM

    更新日期:1994-03-01 00:00:00

  • Structural and immunochemical analysis of three alpha-limit dextrin oligosaccharides.

    abstract::Complete structures are described for three urinary oligodextrins from one patient with type II and one patient with type III glycogen storage disease. GLC-MS, direct probe MS, and 1H NMR demonstrate two heptasaccharides and one hexasaccharide containing only alpha 1-4 and alpha 1-6 linkages. The observation that all ...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(89)90152-5

    authors: Kumlien J,Grönberg G,Nilsson B,Månsson O,Zopf D,Lundblad A

    更新日期:1989-03-01 00:00:00

  • Covalent immobilization of a halophilic, alkalithermostable lipase LipR2 on Florisil® nanoparticles for production of alkyl levulinates.

    abstract::A novel halophilic, alkalithermostable lipase LipR2 from Alkalispirillum sp. NM-ROO2 was cloned and expressed. LipR2 was covalently immobilized on Florisil® functionalized with glutaraldehyde. Protein binding efficiency of functionalized Florisil® was 94.7%. Immobilized LipR2 retained 97.5% of specific activity of the...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/j.abb.2019.04.004

    authors: Mesbah NM

    更新日期:2019-05-30 00:00:00

  • Modification of an essential amino group of phosphoenolpyruvate carboxylase from maize leaves by pyridoxal phosphate and by pyridoxal phosphate-sensitized photooxidation.

    abstract::Phosphoenolpyruvate carboxylase from maize leaves was inactivated by pyridoxal 5'-phosphate in the dark and in the light. A two-step reversible mechanism is proposed for inactivation in the dark, which involves the formation of a noncovalent complex prior to a Schiff base with amino groups of the enzyme. Spectral anal...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(86)90309-7

    authors: Podesta FE,Iglesias AA,Andreo CS

    更新日期:1986-05-01 00:00:00

  • HIV-I TAT inhibits PKR activity by both RNA-dependent and RNA-independent mechanisms.

    abstract::Replication of the human immunodeficiency virus type 1 (HIV-1) is inhibited by interferons (IFNs), in part through activity of the IFN-inducible protein kinase PKR. To escape this antiviral effect, HIV-1 has developed strategies for blocking PKR function. We have previously shown that the HIV-1 Tat protein can associa...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.1999.1583

    authors: Cai R,Carpick B,Chun RF,Jeang KT,Williams BR

    更新日期:2000-01-15 00:00:00

  • Purification and some properties of carbonic anhydrase from bovine skeletal muscle.

    abstract::Procedures for the purification of bovine muscle carbonic anhydrase (isoenzyme III) are described. The purified enzyme has a molecular weight near 29,000 and contains one Zn2+ ion per molecule. The sedimentation coefficient, s(0)20,w, is 2.8 X 10(-13) s, the isoelectric pH is 8.5, and A280(0.1%) = 2.07 cm-1. The CO2 h...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(85)90589-2

    authors: Engberg P,Millqvist E,Pohl G,Lindskog S

    更新日期:1985-09-01 00:00:00

  • Polyphyllin I activates AMPK to suppress the growth of non-small-cell lung cancer via induction of autophagy.

    abstract::Polyphyllin I (PPI), a bioactive constituent extracted from the rhizomes of Paris polyphylla, is cytotoxic to several cancer types. This study was designed to explore whether PPI prevents non-small-cell lung cancer (NSCLC) growth and to investigate the molecular mechanism. AMP-activated protein kinase (AMPK) has been ...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/j.abb.2020.108285

    authors: Wu Y,Si Y,Xiang Y,Zhou T,Liu X,Wu M,Li W,Zhang T,Xiang K,Zhang L,Zhao H,Liu Y

    更新日期:2020-07-15 00:00:00

  • Structure-function relationships in heparin cofactor II: spectral analysis of aromatic residues and absence of a role for sulfhydryl groups in thrombin inhibition.

    abstract::This study characterizes the structural and functional significance of sulfhydryl residues in human plasma heparin cofactor II (HCII). For quantification of sulfhydryl groups, the extinction coefficient of HCII was redetermined and found to be 0.593 ml mg-1 cm-1 using second-derivative spectroscopy and multicomponent ...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1016/0003-9861(87)90499-1

    authors: Church FC,Meade JB,Pratt CW

    更新日期:1987-12-01 00:00:00

  • Reductant-independent ATP hydrolysis catalyzed by homologous nitrogenase proteins from Azotobacter vinelandii and heterologous crosses with Clostridium pasteuranium.

    abstract::Reductant-independent ATPase activity was initiated and studied for Azotobacter vinelandii and Clostridium pasteuranium nitrogenase proteins (Av1, Cp1 and Av2, Cp2, 1 designating the iron molybdenum protein and 2 the iron protein) and their heterologous crosses by two methods: (1) allowing dithionite to be depleted fr...

    journal_title:Archives of biochemistry and biophysics

    pub_type: 杂志文章

    doi:10.1006/abbi.1995.9972

    authors: Larsen C,Christensen S,Watt GD

    更新日期:1995-11-10 00:00:00