Fragile histidine triad protein: structure, function, and its association with tumorogenesis.
BACKGROUND
The human fragile histidine triad (FHIT) gene is a putative tumor suppressor gene, which is located at chromosome region 3p14.2. It was suggested that the loss of heterozygosity (LOH), homozygous deletions, and abnormal expression of the FHIT gene were involved in several types of human malignancies.


METHODS
To determine the role of FHIT in various cancers, we have performed structural and functional analysis of FHIT in detail.


CONCLUSIONS
The protein FHIT catalyzes the Mg(2+) dependent hydrolysis of P1-5 cent-O-adenosine-P3-5 cent-O-adenosine triphosphate, Ap3A, to AMP, and ADP. The reaction is thought to follow a two-step mechanism. Histidine triad proteins, named for a motif related to the sequence H-cent-H-cent-H-cent-cent- (cent, a hydrophobic amino acid), belong to superfamily of nucleotide hydrolases and transferases. This enzyme acts on the R-phosphate of ribonucleotides, and contain a approximately 30-kDa domain that is typically a homodimer of approximately 15 kDa polypeptides with catalytic site.


CONCLUSIONS
Here we have gathered information is known about biological activities of FHIT, the structural and biochemical bases for their functions. Our approach may provide a comparative framework for further investigation of FHIT.
Hassan
Md Imtaiyaz
MI
Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
Naiyer
Abdullah
A
Ahmad
Faizan
F
D017766:Acid Anhydride Hydrolases / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D020022:Genetic Predisposition to Disease; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology*; D009369:Neoplasms / Q000235:genetics*; D010802:Phylogeny; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase