Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary extracted from

  • Davis, J.P.; Copeland, R.A.
    Histidine to alanine mutants of human dihydroorotate dehydrogenase. Identification of a brequinar-resistant mutant enzyme (1997), Biochem. Pharmacol., 54, 459-465.
    View publication on PubMed

Application

EC Number Application Comment Organism
1.3.5.2 medicine molecular target of the antiproliferative, immunosuppressive compound brequinar sodium Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.3.5.2 expressed in Escherichia coli DH5alpha TAP330, lacking the endogenous gene for the bacterial dihydroorotate dehydrogenase, pyrimidine auxotroph Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
1.3.5.2 H11A minimal effect on the relative enzyme activity Homo sapiens
1.3.5.2 H122A minimal effect on the relative enzyme activity Homo sapiens
1.3.5.2 H129A complete loss of enzymatic activity, conserved between the human and rat enzyme, required for enzymatic activity Homo sapiens
1.3.5.2 H218A minimal effect on the relative enzyme activity Homo sapiens
1.3.5.2 H26A minimal effect on the relative enzyme activity, insensitive against brequinar sodium inhibition, suggested location within the brequinar sodium binding pocket, important role in brequinar sodium binding to enzyme Homo sapiens
1.3.5.2 H364A complete loss of enzymatic activity, conserved between the human and rat enzyme, required for enzymatic activity Homo sapiens
1.3.5.2 H56A minimal effect on the relative enzyme activity Homo sapiens
1.3.5.2 H71A complete loss of enzymatic activity, surprising because no conserved residue in the closely related rat enzyme Homo sapiens
1.3.5.2 H71N comparable activity to wild-type, taken together with the results for H71A mutant, the histidine residue is not required at this position, but this site is less permissive than most of the other histidine locations within the enzyme Homo sapiens
1.3.5.2 additional information substitution of all histidine residues by alanine Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.3.5.2 brequinar sodium tight binding, most potent inhibitor, mutant H26A is insensitive, wild-type and other mutants are inhibited by 50% at concentrations between 6 and 10 nM Homo sapiens
1.3.5.2 diethyldicarbonate histidine-selective covalent modifier Homo sapiens
1.3.5.2 leflunomide
-
Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.3.5.2 additional information
-
additional information relative Km-values for wild-type and mutants listed for (S)-dihydroorotate and ubiquinone-6 Homo sapiens
1.3.5.2 0.0155
-
S-dihydroorotate
-
Homo sapiens
1.3.5.2 0.028
-
ubiquinone-6
-
Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.3.5.2 mitochondrion
-
Homo sapiens 5739
-

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
1.3.5.2 39000
-
-
Homo sapiens

Organism

EC Number Organism UniProt Comment Textmining
1.3.5.2 Homo sapiens
-
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.3.5.2 liver
-
Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.3.5.2 (S)-dihydroorotate + acceptor ubiquinone-6 tested as electron acceptor Homo sapiens orotate + reduced acceptor
-
?
1.3.5.2 L-dihydroorotate + ubiquinone-6
-
Homo sapiens orotate + reduced ubiquinone-6
-
?

Synonyms

EC Number Synonyms Comment Organism
1.3.5.2 DHODase
-
Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.3.5.2 23
-
assay at Homo sapiens

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.3.5.2 additional information
-
additional information relative turnover numbers for wild-type and mutants listed for (S)-dihydroorotate and ubiquinone6 Homo sapiens