Structural and kinetic insights into the mechanism of 5-hydroxyisourate hydrolase from Klebsiella pneumoniae.
Summary of "Structural and kinetic insights into the mechanism of 5-hydroxyisourate hydrolase from Klebsiella pneumoniae."
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.
Affiliation
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301, USA.
Journal Details
This article was published in the following journal.
Name: Acta crystallographica. Section D, Biological crystallography
ISSN: 1399-0047
Pages: 671-7
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21795808
- DOI: http://dx.doi.org/10.1107/S090744491101746X
Medical and Biotech [MESH] Definitions
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A hydrolase enzyme that converts L-asparagine and water to L-aspartate and NH3. EC 3.5.1.1.
Dna-formamidopyrimidine Glycosylase
A DNA repair enzyme that is an N-glycosyl hydrolase with specificity for DNA-containing ring-opened N(7)-methylguanine residues.
Chondro-4-sulfatase
An enzyme from the sulfuric ester hydrolase class that breaks down one of the products of the chondroitin lyase II reaction. EC 3.1.6.9.
Lac Operon
The genetic unit consisting of three structural genes, an operator and a regulatory gene. The regulatory gene controls the synthesis of the three structural genes: BETA-GALACTOSIDASE and beta-galactoside permease (involved with the metabolism of lactose), and beta-thiogalactoside acetyltransferase.
Phenytoin
An anticonvulsant that is used in a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.
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