Annotation

Description

Dihydroorotase (DHOase) catalyzes the reversible cyclization of N-carbamyl-l-aspartate (CA-asp) to l-dihydroorotate (DHO), which is third step in the de novo biosynthesis of pyrimidine nucleotides. The pathway is subject to diverse regulatory mechanisms including allosteric inhibition and activation, phosphorylation, and perhaps changes in intracellular location. Understanding the operation and interplay of these controls in the cell remains a fascinating challenge. Modulating the pyrimidine metabolism pharmacologically has therapeutical uses. Pyrimidine synthesis inhibitors are used in active moderate to severe rheumatoid and psoriatic arthritis. Each subunit of the homodimeric enzyme folds into a TIM barrel with eight parallel beta strands in the center and alpha-helices on the outer surface of the molecule. Each subunit contains a binuclear zinc center and carboxylated Lys-103 serving as a bridging ligand between the two cations. Structural studies of apo- and different complexes with ligands and inhibitors revealed importance of the surface loop (residues 106-116), which is involved in the ligand binding.  

Functional assignment

Dihydroorotase 

Structure information

Unit cell parameters

Space Group

P 1 21 1  

Unit Cell

a=50.44Å, b=79.49Å, c=180.61Å
α=90.00, β=90.35, γ=90.00 

Solvent content

43.69  

Matthews coefficient

2.18  

Refinement

Data for the highest resolution shell is in parentheses.

Resolution range

29.83-1.80Å (1.85-1.80Å)  

R_all(%)

16.5 

R_work(%)

16.3 (22.4) 

R_free(%)

20.3 (27.2) 

Num. observed reflections

130156 (9284) 

Num. R_free reflections

6507 (490) 

Completeness(%)

98.5 (95.8) 

Model parameters

Num Atoms

10988  

Num Waters

1328  

Num Hetatoms

1510  

Model mean isotropic B factor

16.320Ų  

RMSD bond length

0.011Å  

RMSD bond angle

1.516°  

Filename uploaded

3JZE.pdb (uploaded on Sep 30, 2009 1:12 PM)  

Inserted

Jul 30, 2009