WordNet

any of the enzymes that catalyze biological oxidation

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/19 15:55:49」(JST)

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Human dihydroorotate dehydrogenase
Identifiers
Symbol	DHODH
Entrez	1723
HUGO	2867
OMIM	126064
PDB	1D3G
RefSeq	NM_001361
UniProt	Q02127
Other data
EC number	1.3.3.1
Locus	Chr. 16 q22

Dihydroorotate dehydrogenase (EC 1.3.3.1) is an enzyme that catalyzes the fourth step in the de novo biosynthesis of pyrimidine. It catalyses the oxidation of dihydroorotate to orotate:

(S)-dihydroorotate + O₂ orotate + H₂O₂

4,5-Dihydroorotic acid
Orotic acid. Note the double bond in the ring.

Human dihydroorotate dehydrogenase is a ubiquitous FMN flavoprotein. In bacteria (gene pyrD), it is located on the inner side of the cytosolic membrane. In some yeasts, such as in Saccharomyces cerevisiae (gene URA1), it is a cytosolic protein, whereas, in other eukaryotes, it is found in the mitochondria.^[1]

Clinical significance

The immunomodulatory drugs teriflunomide and leflunomide have been shown to inhibit DHODH. Human DHODH has two domains: an alpha/beta-barrel domain containing the active site and an alpha-helical domain that forms the opening of a tunnel leading to the active site. Leflunomide has been shown to bind in this tunnel.^[2] Leflunomide is being used for treatment of rheumatoid and psoriatic arthritis.

Mutations in this gene have been shown to cause Miller syndrome ^[3] also known as Genee-Wiedemann syndrome, Wildervanck-Smith syndrome or post axial acrofacial dystosis (POADS).

Model organisms

Model organisms have been used in the study of DHODH function. A conditional knockout mouse line called Dhodh^{tm1b(EUCOMM)Wtsi} was generated at the Wellcome Trust Sanger Institute.^[4] Male and female animals underwent a standardized phenotypic screen^[5] to determine the effects of deletion.^[6]^[7]^[8]^[9] Additional screens performed: - In-depth immunological phenotyping^[10]

*Dhodh* knockout mouse phenotype
Characteristic	Phenotype
All data available at.^[5]^[10]
Peripheral blood leukocytes 6 Weeks	Normal
Insulin	Normal
Haematology 6 Weeks	Normal
Homozygous viability at P14	Abnormal
Recessive lethal study	Abnormal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Cytotoxic T Cell Function	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Bone Marrow Immunophenotyping	Normal

.

References

^ Lacroute F, Thomas D, Nagy M (1992). "Divergent evolution of pyrimidine biosynthesis between anaerobic and aerobic yeasts". Proc. Natl. Acad. Sci. U.S.A. 89 (19): 8966–70. doi:10.1073/pnas.89.19.8966. PMC 50045. PMID 1409592.
^ Liu S, Neidhardt EA, Grossman TH, Ocain T, Clardy J (January 2000). "Structures of human dihydroorotate dehydrogenase in complex with antiproliferative agents". Structure 8 (1): 25–33. doi:10.1016/S0969-2126(00)00077-0. PMID 10673429.
^ Ng SB, Buckingham KJ,Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ (December 2009). "Exome Sequencing identifies the cause of a mendelian disorder". Nature Genetics 42 (1): 30–5. doi:10.1038/ng.499. PMC 2847889. PMID 19915526.
^ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Opthalmologica 88: 925-7.doi:10.1111/j.1755-3768.2010.4142.x: Wiley.
^ ^a ^b "International Mouse Phenotyping Consortium".
^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V et al. (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337â€“42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
^ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9â€“13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
^ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN et al. (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMID 23870131.
^ ^a ^b "Infection and Immunity Immunophenotyping (3i) Consortium".

External links

dihydroorotate dehydrogenase at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the public domain Pfam and InterPro IPR001295

This oxidoreductase article is a stub. You can help Wikipedia by expanding it.

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English Journal

Halomicroarcula pellucida gen. nov., sp. nov., non-pigmented transparent colony-forming halophilic archaeon isolated from solar salt, Sel marin de Guerande, France.

Echigo A, Minegishi H, Shimane Y, Kamekura M, Itoh T, Usami R.SourceToyo University;
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PMID 21378133

Oxygen reactivity in flavoenzymes: context matters.

McDonald CA, Fagan RL, Collard F, Monnier VM, Palfey BA.SourceDepartment of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109-0606, USA.
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Many flavoenzymes--oxidases and monooxygenases--react faster with oxygen than free flavins do. There are many ideas on how enzymes cause this. Recent work has focused on the importance of a positive charge near N5 of the reduced flavin. Fructosamine oxidase has a lysine near N5 of its flavin. We mea
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Japanese Journal

Bifidobacterium bifidum からH_2O_2生産型の NADH oxidase として b-type Dihydroorotate dehydrogenase が精製された

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NAID 10029752600

Isolation of mitochondria from Plasmodium falciparum showing dihydroorotate dependent respiration

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Parasitology international : official journal of the Japanese Society of Parasitology 50(4), 273-278, 2001-11-01
NAID 10009072231

「ジヒドロオロト酸酸化酵素」

	Dihydroorotate dehydrogenase from E. coli
Identifiers
Symbol	DHO_dh
Pfam	PF01180
InterPro	IPR001295
PROSITE	PDOC00708
SCOP	1dor
SUPERFAMILY	1dor
OPM superfamily	59
OPM protein	1uum
CDD	cd02810
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Search
PMC	articles
PubMed	articles
NCBI	proteins

Dihydroorotate oxidase
Identifiers
EC number	1.3.3.1
CAS number	9029-03-2
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search
PMC	articles
PubMed	articles
NCBI	proteins

　　[★]

英: dihydroorotate oxidase
関: ジヒドロオロト酸オキシダーゼ

「ジヒドロオロト酸オキシダーゼ」

　　[★]

英: dihydroorotate oxidase
関: ジヒドロオロト酸酸化酵素

[PUB00004801-1] Lacroute F, Thomas D, Nagy M (1992). "Divergent evolution of pyrimidine biosynthesis between anaerobic and aerobic yeasts". Proc. Natl. Acad. Sci. U.S.A. 89 (19): 8966–70. doi:10.1073/pnas.89.19.8966. PMC 50045. PMID 1409592.

[pmid10673429-2] Liu S, Neidhardt EA, Grossman TH, Ocain T, Clardy J (January 2000). "Structures of human dihydroorotate dehydrogenase in complex with antiproliferative agents". Structure 8 (1): 25–33. doi:10.1016/S0969-2126(00)00077-0. PMID 10673429.

[pmid19915526-3] Ng SB, Buckingham KJ,Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ (December 2009). "Exome Sequencing identifies the cause of a mendelian disorder". Nature Genetics 42 (1): 30–5. doi:10.1038/ng.499. PMC 2847889. PMID 19915526.

[mgp_reference-4] Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Opthalmologica 88: 925-7.doi:10.1111/j.1755-3768.2010.4142.x: Wiley.

[IMPCsearch_ref-5] "International Mouse Phenotyping Consortium".

[pmid21677750-6] Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V et al. (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337â€“42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.

[mouse_library-7] Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.

[mouse_for_all_reasons-8] Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9â€“13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.

[pmid23870131-9] White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN et al. (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMID 23870131.

[iii_ref-10] "Infection and Immunity Immunophenotyping (3i) Consortium".

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dihydroorotate oxidase