1259936-03-2Relevant articles and documents
Conformational study of the natural iron chelator myo-inositol 1,2,3-trisphosphate using restrained/flexible analogues and computational analysis
Mansell, David,Veiga, Nicolás,Torres, Julia,Etchells, Laura L.,Bryce, Richard A.,Kremer, Carlos,Freeman, Sally
, p. 8949 - 8957 (2010)
Myo-Inositol 1,2,3-trisphosphate [Ins(1,2,3)P3], a component in mammalian cells, possesses the correct chemical properties of an intracellular iron transit ligand. Here we have examined the conformation of the Ins(1,2,3)P3-Fe3+ complex. The synthesis and antioxidant properties of 4,6-carbonate-myo-inositol 1,2,3,5-tetrakisphosphate [4,6-carbonate Ins(1,2,3,5)P4], which is locked in the unstable penta-axial chair conformation and 1,2,3-trisphosphoglycerol, a flexible acyclic analogue of Ins(1,2,3)P3, are reported. 4,6-Carbonate Ins(1,2,3,5)P4 caused complete inhibition of iron-catalysed hydroxyl radical (HO?) formation at 100 μM, thereby resembling Ins(1,2,3)P3 and supporting a penta-axial chair binding conformation. In contrast, 1,2,3-trisphosphoglycerol was shown to have incomplete antioxidant properties. In support of experimental observations, we have applied high-level density functional calculations to the binding of Ins(1,2,3)P3 to iron. This study provides evidence that Fe3+ binds tightly to the less stable penta-axial conformation of Ins(1,2,3)P3 using terminal and bridging phosphate oxygens, thought to also contain a tightly bound water molecule or hydroxyl ligand in the complex.
