Words similar to fhit-substrate

Example sentences for: fhit-substrate

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Human Fhit protein, a member of the Fhit branch of the histidine triad superfamily of nucleotide-binding proteins, binds and hydrolyzes diadenosine polyphosphates such as ApppA and AppppA ( 1 ) into AMP plus ADP and ATP, respectively [ 8 9 10 ] . His96, which is responsible for covalent catalysis and more than 4× 10 6-fold of rate enhancement in ApppA hydrolysis [ 9 11 12 13 ] , is nonetheless dispensable for ApppA-binding and tumor suppression, suggesting that Fhit function in tumor suppression depends on formation of an E-S complex [ 2 12 ] . If Fhit-substrate complexes promote tumor suppression by stimulating a pro-apoptotic effector, then Fhit inhibitors that resemble natural substrates may promote Fhit function.
The middle histidine of the histidine triad (His96 in human Fhit), which is critical for hydrolysis of ApppA by Fhit [ 14 16 ] , is not necessary for tumor suppression [ 17 18 ] . Nonetheless, wild-type and His96Asn forms of Fhit are saturated by ApppA in the low micromolar range and form stable complexes with non-hydrolyzable ApppA in which two ApppA analogs are bound per Fhit dimer and all phosphates cluster on one surface of the protein [ 16 ] . These observations suggested that Fhit-substrate complexes may be the active, signaling form of Fhit and that the function of the catalytically essential histidine may be to terminate the lifetime of signaling complexes [ 16 ] .