Crystal structures of HINT demonstrate that histidine triad proteins are GalT-related nucleotide-binding proteins

Nat Struct Biol. 1997 Mar;4(3):231-8. doi: 10.1038/nsb0397-231.


Histidine triad nucleotide-binding protein (HINT), a dimeric purine nucleotide-binding protein from rabbit heart, is a member of the HIT (histidine triad) superfamily which includes HINT homologues and FHIT (HIT protein encoded at the chromosome 3 fragile site) homologues. Crystal structures of HINT-nucleotide complexes demonstrate that the most conserved residues in the superfamily mediate nucleotide binding and that the HIT motif forms part of the phosphate binding loop. Galactose-1-phosphate uridylyltransferase, whose deficiency causes galactosemia, contains tandem HINT domains with the same fold and mode of nucleotide binding as HINT despite having no overall sequence similarity. Features of FHIT, a diadenosine polyphosphate hydrolase and candidate tumour suppressor, are predicted from HINT-nucleotide structures.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Biological Evolution
  • Chromosome Mapping
  • Computer Simulation
  • Crystallography, X-Ray
  • Dimerization
  • Histidine
  • Humans
  • Hydrolases*
  • Models, Molecular
  • Models, Structural*
  • Molecular Sequence Data
  • Myocardium / metabolism
  • Nucleosides / metabolism
  • Nucleotides / metabolism
  • Protein Structure, Secondary*
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / metabolism
  • Rabbits
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Software
  • UTP-Hexose-1-Phosphate Uridylyltransferase / chemistry*
  • UTP-Hexose-1-Phosphate Uridylyltransferase / metabolism


  • Nucleosides
  • Nucleotides
  • Proteins
  • Recombinant Proteins
  • histidine triad protein
  • Histidine
  • UTP-Hexose-1-Phosphate Uridylyltransferase
  • Hydrolases