Dihydroorotate dehydrogenase (quinone), mitochondrial

Function

Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor. Required for UMP biosynthesis via de novo pathway.

Classification

Family (Pfam)

PF01180 DHO_dh

InterPro

Aldolase_TIM, DHO_dehydrogenase, Dihydroorotate_DH_2, Dihydroorotate_DH_cat, Dihydroorotate_DH_CS

Functional cluster

Tubulins & Mitochondrial Metabolic Enzymes

Experimental structures · PDB · 101

• 1D3G X-ray 1.60A
• 1D3H X-ray 1.80A
• 2B0M X-ray 2.00A
• 2BXV X-ray 2.15A
• 2FPT X-ray 2.40A
• 2FPV X-ray 1.80A
• 2FPY X-ray 2.00A
• 2FQI X-ray 1.95A
• 2PRH X-ray 2.40A
• 2PRL X-ray 2.10A
• 2PRM X-ray 3.00A
• 2WV8 X-ray 1.90A
• … and 89 more

A predicted model is available from AlphaFold.

Gene Ontology · 9

• GO:0005743 mitochondrial inner membrane
• GO:0005739 mitochondrion
• GO:0004151 dihydroorotase activity
• GO:0106430 dihydroorotate dehydrogenase (quinone) activity
• GO:0004152 dihydroorotate dehydrogenase activity
• GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process
• GO:0044205 'de novo' UMP biosynthetic process
• GO:0009220 pyrimidine ribonucleotide biosynthetic process
• GO:0006225 UDP biosynthetic process

Disease associations

• postaxial acrofacial dysostosis MONDO:0009903

Drugs targeting this protein · 6

• VIDOFLUDIMUS inhibitor
• ASLAN-003 inhibitor
• BREQUINAR inhibitor
• EMVODODSTAT inhibitor
• LEFLUNOMIDE inhibitor
• TERIFLUNOMIDE inhibitor

Related proteins · sequence + function similarity

• Dihydroorotate dehydrogenase (quinone), mitochondrial 1.00
• Dihydroorotate dehydrogenase (quinone), mitochondrial 0.97
• Dihydroorotate dehydrogenase (quinone), mitochondrial 0.96
• Dihydroorotate dehydrogenase (quinone), mitochondrial 0.94
• Dihydroorotate dehydrogenase (quinone), mitochondrial 0.86
• Dihydroorotate dehydrogenase (quinone), mitochondrial 0.85
• Dihydroorotate dehydrogenase (quinone), mitochondrial 0.85
• Dihydroorotate dehydrogenase (quinone), mitochondrial 0.81
• Dihydroorotate dehydrogenase (quinone), mitochondrial 0.78
• Dihydroorotate dehydrogenase (quinone), mitochondrial 0.76
• Dihydroorotate dehydrogenase (quinone), mitochondrial 0.74
• Dihydroorotate dehydrogenase (quinone), mitochondrial 0.73

Co-cited proteins · studied together in the literature

• Dihydroorotate dehydrogenase (quinone), mitochondrial 1 shared papers

Literature · 12 cited papers

• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Exome sequencing identifies the cause of a Mendelian disorder. Nat. Genet. · 2010
• Dual binding mode of a novel series of DHODH inhibitors. J. Med. Chem. · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• Requirements for the mitochondrial import and localization of dihydroorotate dehydrogenase. Eur. J. Biochem. · 2000
• Structures of human dihydroorotate dehydrogenase in complex with antiproliferative agents. Structure · 2000
• 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. Eur. J. Biochem. · 1996
• Recombinant human dihydroorotate dehydrogenase: expression, purification, and characterization of a catalytically functional truncated enzyme. Arch. Biochem. Biophys. · 1995
• Cloning and sequencing of a human cDNA coding for dihydroorotate dehydrogenase by complementation of the corresponding yeast mutant. Gene · 1992