Structural and kinetic insights into the mechanism of 5-hydroxyisourate hydrolase from Klebsiella pneumoniae

Jarrod B. French, Steven E. Ealick

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

The stereospecific oxidative degradation of uric acid to (S) - allantoin has recently been 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 (HIUH). The high-resolution crystal structure of HIUH from the opportunistic pathogen Klebsiella pneumoniae (KpHIUH) has been determined. KpHIUH is a homotetrameric protein that, based on sequence and structural similarity, belongs to the transthyretin-related protein family. In addition, the steady-state kinetic parameters for this enzyme and four active-site mutants have been measured. These data provide valuable insight into the functional roles of the active-site residues. Based upon the structural and kinetic data, a mechanism is proposed for the KpHIUH-catalyzed reaction.

Original languageEnglish (US)
Pages (from-to)671-677
Number of pages7
JournalActa Crystallographica Section D: Biological Crystallography
Volume67
Issue number8
DOIs
StatePublished - Aug 2011
Externally publishedYes

Keywords

  • Hpx genes
  • purine catabolism
  • transthyretin-like proteins
  • ureides
  • uric acid degradation

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