Steve Ealick's Research Group

Klebsiella pneumoniae 5-Hydroxyisourate Hydrolase

PDB file:



The stereospecific oxidative degradation of uric acid to (S)-allantoin was recently demonstrated to proceed via two unstable intermediates and requires three separate enzymatic reactions.  The second step of this reaction, the conversion of 5-hydroxyisourate (HIU) to 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline, is catalyzed by HIU hydrolase (KpHIUH; HpxT). We have determined the structure of this enzyme and proposed a mechanism for the catalysis. We have also structurally characterized the allantoin racemase (HpxA) and the 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase (HpxQ) from this family.

KpHIUH belongs to the transthyretin related protein family. The protomer consists of nine β-strands and one α-helix organized into a β-sandwich structure.


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The tetramer is a dimer of dimers, with two protomers arranged to create an extended β-sheet that makes up the dimer-dimer interface.  While other HIUH enzymes show some slight differences in conformation between protomers, there is little structural difference between the chains of KpHIUH.

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Similar to other transthyretin-like proteins, KpHIUH possesses two active sites per tetramer that are situated at a dimer interface near the surface of the protein.

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French JB and Ealick SE. Structural and kinetic insights into the mechanism of 5-hydroxyisourate hydrolase from Klebsiella pneumoniae. Acta Crystallogr. D 67:671-677 (2011). PubMed

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