Crystal structures of HINT demonstrate that histidine triad proteins are GalT-related nucleotide-binding proteins.
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.
Brenner
C
C
Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254, USA. brenner@dada.jci.tju.edu
Garrison
P
P
Gilmour
J
J
Peisach
D
D
Ringe
D
D
Petsko
G A
GA
Lowenstein
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D002874:Chromosome Mapping; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D019281:Dimerization; D006639:Histidine; D006801:Humans; D006867:Hydrolases; D008958:Models, Molecular; D008961:Models, Structural; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D009705:Nucleosides / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012984:Software; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000737:chemistry* / Q000378:metabolism
D009705:Nucleosides; D009711:Nucleotides; D011506:Proteins; D011994:Recombinant Proteins; C097552:histidine triad protein; D006639:Histidine; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase; D006867:Hydrolases