2q37
Crystal structure of OHCU decarboxylase in the presence of (S)-allantoin
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OverviewOverview
The ureide pathway, which mediates the oxidative degradation of uric acid, to (S)-allantoin, represents the late stage of purine catabolism in most, organisms. The details of uric acid metabolism remained elusive until the, complete pathway involving three enzymes was recently identified and, characterized. However, the molecular details of the exclusive production, of one enantiomer of allantoin in this pathway are still undefined. Here, we report the crystal structure of, 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) decarboxylase, which, catalyzes the last reaction of the pathway, in a complex with the product, (S)-allantoin, at 2.5-A resolution. The homodimeric helical protein, represents a novel structural motif and reveals that the active site in, each monomer contains no cofactors, distinguishing this enzyme, mechanistically from other cofactor-dependent decarboxylases. On the basis, of structural analysis, along with site-directed mutagenesis, a mechanism, for the enzyme is proposed in which a decarboxylation reaction occurs, directly, and the invariant histidine residue in the OHCU decarboxylase, family plays an essential role in producing (S)-allantoin through a proton, transfer from the hydroxyl group at C4 to C5 at the re-face of OHCU. These, results provide molecular details that address a longstanding question of, how living organisms selectively produce (S)-allantoin.
About this StructureAbout this Structure
2Q37 is a Single protein structure of sequence from Arabidopsis thaliana with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structural and functional basis for (s)-allantoin formation in the ureide pathway., Kim K, Park J, Rhee S, J Biol Chem. 2007 Aug 10;282(32):23457-64. Epub 2007 Jun 13. PMID:17567580
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