Structure of zebra fish HIUase: insights into evolution of an enzyme to a hormone transporter

J Mol Biol. 2006 Oct 13;363(1):1-9. doi: 10.1016/j.jmb.2006.07.079. Epub 2006 Aug 2.


During early vertebrate evolution, a duplication event in the gene encoding 5-hydroxyisourate hydrolase (HIUase), a widely distributed enzyme of purine metabolism, gave rise to transthyretin (TTR), a thyroid hormone transporter. We report here on the crystal structure of zebra fish HIUase in two different crystal forms. Despite the phylogenetic distance, this structure compares well with those of newly characterized bacterial HIUases, especially with regard to catalytic regions, which are highly preserved. Comparison with TTR structure reveals a highly conserved scaffold, harbouring distinct functional sites located in the same regions of the two vertebrate proteins. Residues that are differentially conserved in HIUases compared to TTR map in putative catalytic regions occupying significant portions of the two halves of a central channel that transverses the whole TTR protein. The evolution of TTR has been accompanied by remarkable changes of the HIUase active sites that gave rise to a channel open at both ends, thus allowing free access to hormone molecules.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amidohydrolases / chemistry*
  • Amidohydrolases / metabolism
  • Amino Acid Sequence
  • Animals
  • Biological Transport, Active
  • Crystallography, X-Ray
  • Evolution, Molecular*
  • Humans
  • Molecular Sequence Data
  • Phylogeny
  • Prealbumin / metabolism*
  • Protein Binding
  • Receptors, Albumin / chemistry
  • Receptors, Albumin / metabolism
  • Thyroid Hormones / metabolism*
  • Zebrafish Proteins / chemistry*
  • Zebrafish Proteins / metabolism
  • Zebrafish*


  • Prealbumin
  • Receptors, Albumin
  • Thyroid Hormones
  • Zebrafish Proteins
  • transthyretin receptor
  • Amidohydrolases
  • hydroxyisourate hydrolase

Associated data

  • GENBANK/DQ640307
  • PDB/2H1X
  • PDB/2H6U