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The histidine triad superfamily of nucleotide‐binding proteins
Author(s) -
Brenner Charles,
Bieganowski Pawel,
Pace Helen C.,
Huebner Kay
Publication year - 1999
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199911)181:2<179::aid-jcp1>3.0.co;2-8
Subject(s) - fhit , histidine , biology , biochemistry , nucleotide , peptide sequence , ras superfamily , dna binding protein , triad (sociology) , function (biology) , genetics , amino acid , gene , enzyme , gtp' , transcription factor , carcinogenesis , psychology , tumor suppressor gene , psychoanalysis
Histidine triad (HIT) proteins were until recently a superfamily of proteins that shared only sequence motifs. Crystal structures of nucleotide‐bound forms of histidine triad nucleotide‐binding protein (Hint) demonstrated that the conserved residues in HIT proteins are responsible for their distinctive, dimeric, 10‐stranded half‐barrel structures that form two identical purine nucleotide‐binding sites. Hint‐related proteins, found in all forms of life, and fragile histidine triad (Fhit)‐related proteins, found in animals and fungi, represent the two main branches of the HIT superfamily. Hint homologs are intracellular receptors for purine mononucleotides whose cellular function remains elusive. Fhit homologs bind and cleave diadenosine polyphosphates (Ap n A) such as ApppA and AppppA. Fhit‐Ap n A complexes appear to function in a proapoptotic tumor suppression pathway in epithelial tissues. In invertebrates, Fhit homologs are encoded as fusion proteins with proteins related to plant and bacterial nitrilases that are candidate signaling partners in tumor suppression. J. Cell. Physiol. 181:179–187, 1999. © 1999 Wiley‐Liss, Inc.