EC Number   |
General Information |
Reference |
|---|
    3.5.2.3 | evolution |
despite evolutionary divergence, the CAD DHOase active site components are highly conserved with those in bacterial DHOases, encoded as monofunctional enzymes. An important element for catalysis, conserved from Escherichia coli to humans, is a flexible loop that closes as a lid over the active site. The flexible loop exhibits a two-amino acid signature that is characteristic for each DHOase type |
757206 |
| 3.5.2.3 | evolution |
dihydroorotase (DHO) is an amidohydrolase that catalyzes the reversible condensation of carbamoyl aspartate to form dihydroorotate in de novo pyrimidine biosynthesis in virtually all organisms. Although the same reaction is catalyzed by all DHOs, the structure, oligomeric organization, and metal content of this family of enzymes is diverse |
757192 |
| 3.5.2.3 | evolution |
dihydroorotase (DHOase) is a member of the cyclic amidohydrolase family, which also includes allantoinase, hydantoinase, dihydropyrimidinase (DHPase), and imidase. Almost all of these zinc metalloenzymes possess a binuclear metal center in which two metal ions are bridged by a post-translational carbamylated Lys |
755973 |
| 3.5.2.3 | evolution |
mammals have a large, multifunctional dihydroorotate synthetase (CAD) enzyme for the first three steps of the de novo pyrimidine biosynthesis pathway, while prokaryotes use three separate monofunctional enzymes for each. DHOase is divided into two evolutionary classes, with very low sequence identity (< 30%) between classes. Class I DHOases are found in gram-positive bacteria, mold, and insects, while Class II DHOases are found in gram-negative bacteria and fungi. The major structural difference between the Class I and Class II DHOase is the longer catalytic loop of Class II counterparts |
-, 756175 |
| 3.5.2.3 | evolution |
the enzyme belongs to the amidohydrolase superfamily |
-, 756119, 756957 |
| 3.5.2.3 | evolution |
the structure of YpDHO has essentially the same conformation as the structure of DHO from Escherichia coli (EcDHO), the most thoroughly studied bacterial type II DHO. The enzyme belongs to the amidohydrolase superfamily |
756957 |
| 3.5.2.3 | malfunction |
a huDHOase chimera bearing the Escherichia coli DHOase flexible loop is inactive, suggesting the presence of distinctive elements in the flexible loop of huDHOase that cannot be replaced by the bacterial sequence. Substitutions of Phe1563 with Ala, Leu, or Thr prevent the closure of the flexible loop and inactivated the protein, whereas substitution with Tyr enhances the interactions of the loop in the closed position and reduced fluctuations and the reaction rate |
757206 |
| 3.5.2.3 | malfunction |
a parallel salvage pathway of pyrimidine biosynthesis exists, since kaempferol cannot completely inhibit the pathway in vivo |
-, 756119 |
| 3.5.2.3 | malfunction |
the replacement of the zinc ligand Cys181 with glycine does not restore the latent catalytic activity suggesting that it plays a minor role in stabilizing loop A |
756707 |
| 3.5.2.3 | metabolism |
catalyzes the conversion of N-carbamoyl-L-aspartate to dihydroorotate in the third step of the de novo biosynthesis of pyrimidines |
-, 758285 |
