2O70
Structure of OHCU decarboxylase from zebrafish
Summary for 2O70
| Entry DOI | 10.2210/pdb2o70/pdb |
| Related | 2O73 2O74 |
| Descriptor | OHCU decarboxylase (2 entities in total) |
| Functional Keywords | uric acid, decarboxylation, 5-hydroxyisourate, allantoin, lyase |
| Biological source | Danio rerio (zebrafish) |
| Cellular location | Peroxisome (Probable): A1L259 |
| Total number of polymer chains | 6 |
| Total formula weight | 118611.87 |
| Authors | Cendron, L.,Berni, R.,Folli, C.,Ramazzina, I.,Percudani, R.,Zanotti, G. (deposition date: 2006-12-09, release date: 2007-04-10, Last modification date: 2023-12-27) |
| Primary citation | Cendron, L.,Berni, R.,Folli, C.,Ramazzina, I.,Percudani, R.,Zanotti, G. The structure of 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase provides insights into the mechanism of uric acid degradation. J.Biol.Chem., 282:18182-18189, 2007 Cited by PubMed Abstract: The complete degradation of uric acid to (S)-allantoin, as recently elucidated, involves three enzymatic reactions. Inactivation by pseudogenization of the genes of the pathway occurred during hominoid evolution, resulting in a high concentration of urate in the blood and susceptibility to gout. Here, we describe the 1.8A resolution crystal structure of the homodimeric 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase, which catalyzes the last step in the urate degradation pathway, for both ligand-free enzyme and enzyme in complex with the substrate analogs (R)-allantoin and guanine. Each monomer comprises ten alpha-helices, grouped into two domains and assembled in a novel fold. The structure and the mutational analysis of the active site have allowed us to identify some residues that are essential for catalysis, among which His-67 and Glu-87 appear to play a particularly significant role. Glu-87 may facilitate the exit of the carboxylate group because of electrostatic repulsion that destabilizes the ground state of the substrate, whereas His-67 is likely to be involved in a protonation step leading to the stereoselective formation of the (S)-allantoin enantiomer as reaction product. The structural and functional characterization of 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase can provide useful information in view of the potential use of this enzyme in the enzymatic therapy of gout. PubMed: 17428786DOI: 10.1074/jbc.M701297200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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