Completing the uric acid degradation pathway through phylogenetic comparison of whole genomes

@article{Ramazzina2006CompletingTU,
  title={Completing the uric acid degradation pathway through phylogenetic comparison of whole genomes},
  author={Ileana Ramazzina and Claudia Folli and Andrea Secchi and Rodolfo Berni and Riccardo Percudani},
  journal={Nature Chemical Biology},
  year={2006},
  volume={2},
  pages={144-148}
}
Mammals that degrade uric acid are not affected by gout or urate kidney stones. It is not fully understood how they convert uric acid into the much more soluble allantoin. Until recently, it had long been thought that urate oxidase was the only enzyme responsible for this conversion1,2. However, detailed studies of the mechanism and regiochemistry of urate oxidation3,4,5 have called this assumption into question, suggesting the existence of other distinct enzymatic activities. Through… Expand
The ygeW encoded protein from Escherichia coli is a knotted ancestral catabolic transcarbamylase
TLDR
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Evolutionary history and metabolic insights of ancient mammalian uricases
Significance Human susceptibility to gout is driven by the fact that we have a pseudogene for uricase that prevents a functional enzyme from being produced. Our inability to convert highly insolubleExpand
Mouse transthyretin-related protein is a hydrolase which degrades 5-hydroxyisourate, the end product of the uricase reaction.
TLDR
Evidence is provided that mouse transthyretin-related protein facilitates the hydrolysis of 5-hydroxyisourate, the end product of the uricase reaction, and it is proposed that the tranSTH-related proteins present in diverse organisms are not functionally related to tran STH but actually function as hydroxy isourate hydrolases. Expand
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TLDR
The results indicate that the last functioning Uox in hominoid evolution had an increased Michaelis constant, possibly near to upper end of the normal range of urate in the human serum (~300 μM). Expand
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TLDR
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TLDR
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The identification of an integral membrane, cytochrome c urate oxidase completes the catalytic repertoire of a therapeutic enzyme
TLDR
The findings identify a missing link in purine catabolism, assign a biochemical activity to a domain of unknown function (DUF989), and complete the catalytic repertoire of an enzyme useful for human therapy. Expand
Structural and functional basis for (S)-allantoin formation in the ureide pathway
TLDR
The crystal structure of the OHCU decarboxylase family, which catalyzes the last reaction of the ureide pathway, is reported, providing molecular details that address a longstanding question of how living organisms selectively produce (S)-allantoin. Expand
The Structure of 2-Oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline Decarboxylase Provides Insights into the Mechanism of Uric Acid Degradation*
TLDR
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 and can provide useful information in view of the potential use of this enzyme in the enzymatic therapy of gout. Expand
Walking on the ureide pathway
S-allantoin, a major ureide compound, is produced in plant peroxisomes through degradation of oxidised purines. Fundamental information is missing on the enzymes and regulation of the plant pathway.Expand
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It is suggested that amphibian urate oxidase is a transition form in the evolution of aquatic animals to land animals, and changes of allantoinase and allantoicase in molecular structure and intracellular localization during animal evolution may be as follows. Expand
Transthyretin‐related proteins function to facilitate the hydrolysis of 5‐hydroxyisourate, the end product of the uricase reaction
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Evidence is provided that PucM, a transthyretin‐related protein, functions to facilitate the hydrolysis of 5‐hydroxyisourate, the end product of the uricase reaction. Expand
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The identification and purification of a novel enzyme from soybean root nodules that catalyzes the hydrolysis of 5-hydroxyisourate and the existence of a hitherto unrecognized enzymatic pathway for the formation of allantoin is suggested. Expand
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Functional Analysis of 14 Genes That Constitute the Purine Catabolic Pathway in Bacillus subtilis and Evidence for a Novel Regulon Controlled by the PucR Transcription Activator
TLDR
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