Words similar to fhit-substrate

Example sentences for: fhit-substrate

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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 ] .
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.