Literature summary for 1.3.5.2 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.

Search for more literature for 1.3.5.2

Application

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

Cloned(Commentary)

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

Protein Variants

Protein Variants	Comment	Organism
H11A	minimal effect on the relative enzyme activity	Homo sapiens
H122A	minimal effect on the relative enzyme activity	Homo sapiens
H129A	complete loss of enzymatic activity, conserved between the human and rat enzyme, required for enzymatic activity	Homo sapiens
H218A	minimal effect on the relative enzyme activity	Homo sapiens
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
H364A	complete loss of enzymatic activity, conserved between the human and rat enzyme, required for enzymatic activity	Homo sapiens
H56A	minimal effect on the relative enzyme activity	Homo sapiens
H71A	complete loss of enzymatic activity, surprising because no conserved residue in the closely related rat enzyme	Homo sapiens
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
additional information	substitution of all histidine residues by alanine	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
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
diethyldicarbonate	histidine-selective covalent modifier	Homo sapiens
leflunomide	-	Homo sapiens

KM Value [mM]

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

Localization

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

Molecular Weight [Da]

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

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
liver	-	Homo sapiens	-

Substrates and Products (Substrate)

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

Synonyms

Synonyms	Comment	Organism
DHODase	-	Homo sapiens

Temperature Optimum [°C]

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

Turnover Number [1/s]

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

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Release 2023.1 (January 2023)