UniProtKB Q02127 (PYRD_HUMAN) - Dihydroorotate dehydrogenase (quinone), mitochondrial
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Curated UniProt record for human DHODH; source of catalytic activity, cofactor, pathway, subcellular location, and disease annotations
"Catalyzes the conversion of dihydroorotate to orotate with"
Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
Functional expression of a fragment of human dihydroorotate dehydrogenase by means of the baculovirus expression vector system, and kinetic investigation of the purified recombinant enzyme.
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Demonstrated recombinant human DHODH uses ubiquinone as electron acceptor
"By kinetics analysis, Km values for dihydroorotate and ubiquinone-50 were found to be 4 microM and 9.9 microM, respectively"
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Determined Km values for dihydroorotate (4 uM) and ubiquinone-50 (9.9 uM)
"Km values for dihydroorotate and ubiquinone-50 were found to be 4 microM and 9.9 microM, respectively, while Km values for dihydroorotate and decylubiquinone were 9.4 microM and 13.7 microM"
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Confirmed FMN as the prosthetic group by fluorimetric analysis
"Fluorimetric cofactor analysis revealed the presence of FMN in recombinant dihydroorotate dehydrogenase"
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Established IC50 of 1 uM for A77 1726 (teriflunomide active metabolite)
"An IC50 value of 1 microM was determined for A77 1726"
Structures of human dihydroorotate dehydrogenase in complex with antiproliferative agents.
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Crystal structure at 1.6A resolution showing FMN binding
"The structures have been refined to crystallographic R factors of 16.8% and 16.2% at resolutions of 1. 6 A and 1.8 A"
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Identified inhibitor binding site in ubiquinone tunnel
"an alpha-helical domain that forms the opening of a tunnel leading to the active site. Both inhibitors share a common binding site in this tunnel"
A reference map of the human binary protein interactome.
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High-throughput Y2H study detecting binary protein interactions
"The dataset, versioned HI-III-20 (Human Interactome obtained from screening Space III, published in 2020), contains 52,569 verified PPIs involving 8,275 proteins"
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
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Defined MitoCoP - high-confidence human mitochondrial proteome of 1,134 proteins
"defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)"
DHODH:FMN oxidises (S)-DHO to orotate
DHODH:FMN binds DHODH inhibitors
DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer.
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DHODH produces CoQH2 which acts as radical-trapping antioxidant in mitochondria
"Mechanistically, DHODH operates in parallel to mitochondrial GPX4 (but independently of cytosolic GPX4 or FSP1) to inhibit ferroptosis in the mitochondrial inner membrane by reducing ubiquinone to ubiquinol"
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DHODH operates in parallel to GPX4 and FSP1 to suppress ferroptosis
"DHODH operates in parallel to mitochondrial GPX4 (but independently of cytosolic GPX4 or FSP1) to inhibit ferroptosis"
Deep research report on human DHODH gene function
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Comprehensive review of DHODH function, localization, and clinical relevance
"Human DHODH (Q02127) is a mitochondrially embedded, ubiquinone-dependent flavoenzyme"
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DHODH role in respiratory chain coupling
"DHODH's respiratory-chain coupling via ubiquinone and membrane tunnel is well established and central to its physiology and pharmacology"