{PDOC00401}
{PS00482; DIHYDROOROTASE_1}
{PS00483; DIHYDROOROTASE_2}
{BEGIN}
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* Dihydroorotase signatures *
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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.

-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.

-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.

-Last update: December 2004 / Pattern and text revised.

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

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