PROSITE documentation PDOC00401

Dihydroorotase signatures

Description

Dihydroorotase (EC 3.5.2.3) (DHOase) catalyzes the third step in the de novo biosynthesis of pyrimidine, the conversion of ureidosuccinic acid (N-carbamoyl-L-aspartate) into dihydroorotate. Dihydroorotase binds a zinc ion which is required for its catalytic activity [1].

In bacteria, DHOase is a dimer of identical chains of about 400 amino-acid residues (gene pyrC). In higher eukaryotes, DHOase is part of a large multi-functional protein known as 'rudimentary' in Drosophila and CAD in mammals and which catalyzes the first three steps of pyrimidine biosynthesis [2]. The DHOase domain is located in the central part of this polyprotein. In yeasts, DHOase is encoded by a monofunctional protein (gene URA4). However, a defective DHOase domain [3] is found in a multifunctional protein (gene URA2) that catalyzes the first two steps of pyrimidine biosynthesis.

The comparison of DHOase sequences from various sources shows [4] that there are two highly conserved regions. The first located in the N-terminal extremity contains two histidine residues suggested [3] to be involved in binding the zinc ion. The second is found in the C-terminal part. We developed signature patterns for both regions.

Allantoinase (EC 3.5.2.5) is the enzyme that hydrolyzes allantoin into allantoate. In yeast (gene DAL1) [5], it is the first enzyme in the allantoin degradation pathway; in amphibians [6] and fishs it catalyzes the second step in the degradation of uric acid. The sequence of allantoinase is evolutionary related to that of DHOases.

Last update:

December 2004 / Pattern and text revised.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

DIHYDROOROTASE_1, PS00482; Dihydroorotase signature 1  (PATTERN)
Consensus pattern: D-[LIVMFYWSAP]-H-[LIVA]-H-[LIVF]-[RN]-x-[PGANF]
The 2 H's may be zinc ligands
Sequences known to belong to this class detected by the pattern: ALL, except Drosophila rud and two bacterial pyrC
Other sequence(s) detected in Swiss-Prot: 3.
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00482
• Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00482
• Scan Swiss-Prot/TrEMBL entries against PS00482
• view ligand binding statistics
Matching PDB structures: 1J79 1XGE 1XRF 1XRT ... [ALL]
DIHYDROOROTASE_2, PS00483; Dihydroorotase signature 2  (PATTERN)
Consensus pattern: [GAVS]-[ST]-D-x-A-P-H-x(4)-K
Sequences known to belong to this class detected by the pattern: ALL, except for allantoinases
Other sequence(s) detected in Swiss-Prot: NONE.
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00483
• Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00483
• Scan Swiss-Prot/TrEMBL entries against PS00483
• view ligand binding statistics
Matching PDB structures: 1J79 1XGE 2E25 2EG6 ... [ALL]

References

1 Authors Brown D.C., Collins K.D.
Title Dihydroorotase from Escherichia coli. Substitution of Co(II) for the active site Zn(II).
Source J. Biol. Chem. 266:1597-1604(1991).
PubMed ID 1671037
2 Authors Davidson J.N., Chen K.C., Jamison R.S., Musmanno L.A., Kern C.B.
Title The evolutionary history of the first three enzymes in pyrimidine biosynthesis.
Source BioEssays 15:157-164(1993).
PubMed ID 8098212
3 Authors Souciet J.-L., Nagy M., Le Gouar M., Lacroute F., Potier S.
Title Organization of the yeast URA2 gene: identification of a defective dihydroorotase-like domain in the multifunctional carbamoylphosphate synthetase-aspartate transcarbamylase complex.
Source Gene 79:59-70(1989).
PubMed ID 2570735
4 Authors Guyonvarch A., Nguyen-Juilleret M., Hubert J.-C., Lacroute F.
Title Structure of the Saccharomyces cerevisiae URA4 gene encoding dihydroorotase.
Source Mol. Gen. Genet. 212:134-141(1988).
PubMed ID 2897615
5 Authors Buckholz R.G., Cooper T.G.
Title The allantoinase (DAL1) gene of Saccharomyces cerevisiae.
Source Yeast 7:913-923(1991).
PubMed ID 1803816
6 Authors Hayashi S., Jain S., Chu R., Alvares K., Xu B., Erfurth F., Usuda N., Rao M.S., Reddy S.K., Noguchi T.
Title Amphibian allantoinase. Molecular cloning, tissue distribution, and functional expression.
Source J. Biol. Chem. 269:12269-12276(1994).
PubMed ID 8163532

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