2O74

Structure of OHCU decarboxylase in complex with guanine

Summary for 2O74

• Entry DOI: 10.2210/pdb2o74/pdb
• Related: 2O70 2O73
• Descriptor: OHCU decarboxylase, GUANINE (3 entities in total)
• Functional Keywords: decarboxylation, ohcu, 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline, hiu, 5-hydroxyisourate, lyase
• Biological source: Danio rerio (zebrafish)
• Cellular location: Peroxisome (Probable): A1L259
• Total number of polymer chains: 6
• Total formula weight: 119518.63

Authors

Cendron, L.,Berni, R.,Folli, C.,Ramazzina, I.,Percudani, R.,Zanotti, G. (deposition date: 2006-12-10, release date: 2007-04-10, Last modification date: 2023-10-25)

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

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: 17428786
DOI: 10.1074/jbc.M701297200

Experimental method

X-RAY DIFFRACTION (1.8 Å)