The mechanism of iron transferrin interactions. Uptake of the iron nitrilotriacetic acid complex

Abstract
The role of the protonation of the transferrin amino acid ligands involved in complex formation with iron in the presence of nitrilotriacetate has been elucidated. The C-terminal site of transferrin binds to Fe(nta) to produce FeH3Tc; second-order rate constant k1=(7.00 ± 0.05)× 103 dm3 mol–1 s–1, stability constant K1(1.00 ± 0.10)× 10–5 mol dm–3. This lowers the deprotonation pKa of probably the phenolic side-chain of one tyrosine which loses a proton and, thereby, leads to FeH2Tc; dissociation constant K1a=(4.50 ± 0.50)× 10–7 mol dm–3 and a possible complex stability constant K1′≈ 2.3 × 10–9 mol dm–3. As for the N-terminal site, it binds to Fe(nta) by a process controlled by a slow proton transfer; second-order rate constant k2a=(4.50 ± 0.30)× 106 dm3 mol–1 s–1, a reverse rate constant k–2= 0.40 ± 0.05 s–1, proton dissociation constant K2a=(8.5 ± 1.1)× 10–8 mol dm–3. It remains to be shown whether this slow proton transfer controls a change of the conformation of the binding site or if it occurs because of the particular conformations of the binding sites in neutral media.

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