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 Biophysjournal_title
Archives of biochemistry and biophysicsauthors
Reis RAG,Calil FA,Feliciano PR,Pinheiro MP,Nonato MCdoi
10.1016/j.abb.2017.06.019subject
Has Abstractpub_date
2017-10-15 00:00:00pages
175-191eissn
0003-9861issn
1096-0384pii
S0003-9861(17)30272-2journal_volume
632pub_type
杂志文章,评审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
更新日期:1994-06-01 00:00:00
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
更新日期:1994-04-01 00:00:00
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
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章,评审
doi:10.1006/abbi.2000.2253
更新日期:2001-03-01 00:00:00
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
更新日期:2000-08-01 00:00:00
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
更新日期:1991-04-01 00:00:00
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
更新日期:2001-08-01 00:00:00
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
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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
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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
更新日期:2012-10-15 00:00:00
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
更新日期:1993-07-01 00:00:00
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
更新日期:1985-02-15 00:00:00
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
更新日期:2013-10-15 00:00:00
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
更新日期:1998-11-15 00:00:00
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
更新日期:2017-12-15 00:00:00
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
更新日期:1991-10-01 00:00:00
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
更新日期:2004-03-01 00:00:00
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
更新日期:1990-09-01 00:00:00
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
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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
更新日期:1987-11-15 00:00:00
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1006/abbi.1998.0704
更新日期:1998-07-01 00:00:00
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
更新日期:1994-03-01 00:00:00
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
更新日期:1989-03-01 00:00:00
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
更新日期:2019-05-30 00:00:00
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
更新日期:1986-05-01 00:00:00
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
更新日期:2000-01-15 00:00:00
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
更新日期:1985-09-01 00:00:00
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
更新日期:2020-07-15 00:00:00
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
更新日期:1987-12-01 00:00:00
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
更新日期:1995-11-10 00:00:00