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Dihydroorotate dehydrogenase

dihydroorotate dehydrogenase, DHODH, Dihydroorotate Oxidase
The protein encoded by this gene catalyzes the fourth enzymatic step, the ubiquinone-mediated oxidation of dihydroorotate to orotate, in de novo pyrimidine biosynthesis. This protein is a mitochondrial protein located on the outer surface of the inner mitochondrial membrane. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: ACID, STEP, CAN, HAD, Aspartate Carbamoyltransferase
Papers on dihydroorotate dehydrogenase
Comparative study between 3D-QSAR and Docking-Based Pharmacophore models for potent Plasomodium falciparum dihydroorotate dehydrogenase inhibitors.
New
Tsai et al., Taipei, Taiwan. In Bioorg Med Chem Lett, Feb 2016
Nowadays, Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) was validated as a potent drug target to inhibit malarial activity by blocking pyrimidine biosynthesis.
The mechanistic study of Leishmania major dihydroorotate dehydrogenase based on steady- and pre-steady state kinetic analysis.
New
Nonato et al., Ribeirão Preto, Brazil. In Biochem J, Jan 2016
UNASSIGNED: Leishmania major dihydroorotate dehydrogenase (DHODHLm) is considered a potential therapeutic target against leishmaniases.
Identification of a small molecule that simultaneously suppresses virulence and antibiotic resistance of Pseudomonas aeruginosa.
New
Wu et al., Tianjin, China. In Sci Rep, Dec 2015
Next, we employed a computer-aided screening to identify potential inhibitors of the PyrD protein, a dihydroorotate dehydrogenase (DHODase) involved in pyrimidine biosynthesis.
Quantitation of Teriflunomide in Human Serum/Plasma Across a 40,000-Fold Concentration Range by LC/MS/MS.
New
Johnson-Davis et al., Salt Lake City, United States. In Methods Mol Biol, Dec 2015
The active metabolite, teriflunomide (A77 1726), inhibits the enzyme dihydroorotate dehydrogenase and thereby reduces the synthesis of pyrimidine ribonucleotides.
Evaluation of the leishmanicidal and cytotoxic effects of inhibitors for microorganism metabolic pathway enzymes.
New
Giorgio et al., Campinas, Brazil. In Biomed Pharmacother, Aug 2015
In this report, leishmanicidal activity of the metabolic pathway enzymes inhibitors (IDs) of dihydroorotate dehydrogenase (DHODH), glyceraldehyde 3-phosphate dehydrogenase and cruzain-cysteine protease from T. cruzi and scitalona-desidratase, adenosine deaminase, succinate dehydrogenase complex II and hydroxynaphthalene reductase from S. cerevisiae was performed on Leishmania amazonensis extracellular promastigotes and amastigotes within macrophages.
Orotic Acid, More Than Just an Intermediate of Pyrimidine de novo Synthesis.
Review
New
Zameitat et al., Marburg an der Lahn, Germany. In J Genet Genomics, Jun 2015
Recent genetic data link human Miller syndrome to defects in the dihydroorotate dehydrogenase (DHODH) gene, hence to depleted orotate production.
Genetic polymorphisms in metabolic pathways of leflunomide in the treatment of rheumatoid arthritis.
Review
New
Pavek et al., Praha, Czech Republic. In Clin Exp Rheumatol, May 2015
In case of dihydroorotate dehydrogenase (DHODH) gene SNP (rs3213422, 19C>A), it was shown that C allele may be associated with LEF toxicity and therapeutic effect.
[Stimulation of the antiviral innate immune response by pyrimidine biosynthesis inhibitors: a surprise of phenotypic screening].
Review
Munier-Lehmann et al., Paris, France. In Med Sci (paris), 2015
While deciphering its mode of action, DD264 was found to target the fourth enzyme of de novo pyrimidine biosynthesis, namely the dihydroorotate dehydrogenase (DHODH).
Rational Design of Benzylidenehydrazinyl-Substituted Thiazole Derivatives as Potent Inhibitors of Human Dihydroorotate Dehydrogenase with in Vivo Anti-arthritic Activity.
Li et al., Shanghai, China. In Sci Rep, 2014
Human dihydroorotate dehydrogenase (hDHODH) is an attractive therapeutic target for the treatment of rheumatoid arthritis, transplant rejection and other autoimmune diseases.
Teriflunomide for the treatment of relapsing-remitting multiple sclerosis: patient preference and adherence.
Review
Mäurer et al., Augsburg, Germany. In Patient Prefer Adherence, 2014
With teriflunomide, a reversible inhibitor of the enzyme dihydroorotate dehydrogenase, a new oral therapeutic option, given once daily, has been approved within the last 2 years by the regulatory agencies.
Novel inhibitors of the Plasmodium falciparum electron transport chain.
Review
O'Neill et al., Liverpool, United Kingdom. In Parasitology, 2014
Efforts have been focused on targeting key processes along the parasite ETC specifically the dihydroorotate dehydrogenase (DHOD) enzyme, the cytochrome bc 1 enzyme and the NADH type II oxidoreductase (PfNDH2) pathway.
DHODH modulates transcriptional elongation in the neural crest and melanoma.
Impact
GeneRIF
Zon et al., Boston, United States. In Nature, 2011
DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies
Dihydroorotate dehydrogenase is required for N-(4-hydroxyphenyl)retinamide-induced reactive oxygen species production and apoptosis.
GeneRIF
Shearn et al., Aurora, United States. In Free Radic Biol Med, 2010
required for N-(4-hydroxyphenyl)retinamide-induced reactive oxygen species production and apoptosis of cancer epithelial cells
Region-specific distribution of dihydroorotate dehydrogenase in the rat central nervous system points to pyrimidine de novo synthesis in neurons.
GeneRIF
Löfflerr et al., Marburg an der Lahn, Germany. In Nucleosides Nucleotides Nucleic Acids, 2010
High levels of both DHODH activity and immunoreactivity were observed in the neocortex, hippocampus, spinal cord and choroid plexus; lower levels were seen in the cerebellum, and only marginal expression in brainstem
Analysis of genetic inheritance in a family quartet by whole-genome sequencing.
Impact
GeneRIF
Galas et al., Seattle, United States. In Science, 2010
DHODH recessively causes Miller syndrome.
Exome sequencing identifies the cause of a mendelian disorder.
Impact
GeneRIF
Bamshad et al., Seattle, United States. In Nat Genet, 2010
Data confirmed the presence of DHODH mutations in families with Miller syndrome.
Exome sequencing makes medical genomics a reality.
Impact
Biesecker, In Nat Genet, 2010
Massively parallel sequencing of the exomes of four individuals with Miller syndrome, combined with filtering to exclude benign and unrelated variants, has identified causative mutations in DHODH.
Specific role of mitochondrial electron transport in blood-stage Plasmodium falciparum.
Impact
Vaidya et al., Philadelphia, United States. In Nature, 2007
Here we show that erythrocytic stages of the human malaria parasite Plasmodium falciparum seem to maintain an active mitochondrial electron transport chain to serve just one metabolic function: regeneration of ubiquinone required as the electron acceptor for dihydroorotate dehydrogenase, an essential enzyme for pyrimidine biosynthesis.
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