title: Unusual features for zirconium(IV) binding to human serum transferrin.
abstract: Human serum apotransferrin (hTF) binds to Zr(IV) slowly in the presence of nitrilotriacetate (NTA), citrate or ethylenediaminetetraacetate (EDTA) as donor ligands. For Zr(NTA)(2)(2-) as donor, equilibrium was reached in ca. 2 h (pH 7.4, 298 K, 10 mM Hepes, 5 mM bicarbonate) and full loading of the N- and C-lobe sites was achievable to give Zr(2)-hTF. (13)C NMR data suggest that carbonate can bind as a synergistic anion. (1)H and 2D [(1)H,(13)C] (using epsilon-[(13)C]Met-hTF) NMR studies show that there is little lobe-selectively in the order of Zr(IV) uptake. Fe(III) displaced Zr(IV) from the C-lobe of Zr(2)-hTF first, followed by the N-lobe. However, in the presence of a large excess of NTA, Zr(IV) binds to the N-lobe of holo-hTF (Fe(2)-hTF) first followed by the C-lobe. The (1)H and (13)C NMR chemical shift changes for epsilon-[(13)CH(3)] of Met464, which is close to the C-lobe site, are quite distinct from those observed previously for Al(III), Fe(III), Ti(IV), Ga(III) and Bi(III) binding to hTF, suggesting that Zr(IV) binding may not induce lobe closure [as observed previously for Hf(IV)]. This may affect receptor recognition and play a role in the different biological behaviour of Zr(IV) compared to Ti(IV).
authors.affiliation: Department of Chemistry, The University of Edinburgh, King's Buildings, West Mains Road, UK.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Zhong
authors.forename: John A
authors.initials: JA
authors.lastname: Parkinson
authors.forename: Maolin
authors.initials: M
authors.lastname: Guo
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sadler
mesh_terms: D001665:Binding Sites; D001667:Binding, Competitive; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008024:Ligands; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D013054:Spectrophotometry, Atomic / Q000379:methods; D013056:Spectrophotometry, Ultraviolet; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism*; D015040:Zirconium / Q000737:chemistry / Q000378:metabolism*
chemical_list: D005290:Ferric Compounds; D008024:Ligands; D011994:Recombinant Proteins; D014168:Transferrin; D015040:Zirconium