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

Nature Structural Biology volume 4, pages 231–238 (1997)Cite this article

Abstract

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.

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Author notes

  1. Charles Brenner

    Present address: Kimmel Cancer Institute, Thomas Jefferson University, 233 S10th Street, rm 833a, Philadelphia, Pennsylvania, 19107, USA

Authors and Affiliations

  1. Departments of Biochemistry and Chemistry and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts, 02254, USA

    Charles Brenner, Daniel Peisach, Dagmar Ringe & Gregory A. Petsko

  2. Department of Biochemistry, University of Texas Health Sciences Center, San Antonio, Texas, 78284, USA

    Preston Garrison

  3. Department of Biochemistry, Brandeis University, Waltham, Massachusetts, 02254, USA

    Jeffrey Gilmour & John M. Lowenstein

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Brenner, C., Garrison, P., Gilmour, J. et al. Crystal structures of HINT demonstrate that histidine triad proteins are GalT-related nucleotide-binding proteins. Nat Struct Mol Biol 4, 231–238 (1997). https://doi.org/10.1038/nsb0397-231

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