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- *****************************
- * Dihydroorotase signatures *
- *****************************
-
- 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 pyrG). 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.
-
- Yeast allantoinase (EC 3.5.2.5) (gene DAL1) [5] is the first enzyme in the
- allantoin degradation pathway; it hydrolyzes allantoin into allantoate. The
- sequence of DAL1 is evolutionary related to that of DHOases.
-
- -Consensus pattern: D-[LIVMFYWS]-H-[LIV]-H-[LIVF]-[RN]-x-[PG]
- [The two H's are probable zinc ligands]
- -Sequences known to belong to this class detected by the pattern: ALL, except
- Drosophila rud.
- -Other sequence(s) detected in SWISS-PROT: NONE.
-
- -Consensus pattern: [GA]-[ST]-D-x-A-P-H-x(4)-K
- -Sequences known to belong to this class detected by the pattern: ALL, except
- for allantoinase.
- -Other sequence(s) detected in SWISS-PROT: NONE.
-
- -Last update: October 1993 / Patterns and text revised.
-
- [ 1] Brown D.C., Collins K.D.
- J. Biol. Chem. 266:1597-1604(1991).
- [ 2] Davidson J.N., Chen K.C., Jamison R.S., Musmanno L.A., Kern C.B.
- BioEssays 15:157-164(1993).
- [ 3] Souciet J.-L., Nagy M., Le Gouar M., Lacroute F., Potier S.
- Gene 79:59-70(1989).
- [ 4] Guyonvarch A., Nguyen-Juilleret M., Hubert J.-C., Lacroute F.
- Mol. Gen. Genet. 212:134-141(1988).
- [ 5] Buckholz R.G., Cooper T.G.
- Yeast 7:913-923(1991).
-