Uptake of Al3+ into the N-lobe of human serum transferrin

Kubal, Gina; Mason, Anne B.; Sadler, Peter J.; Tucker, Alan; Woodworth, Robert C.

doi:10.1042/bj2850711

Cited by 36 publications

(35 citation statements)

References 17 publications

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“…High fieldshifted resonances have been assigned to protons from residues around Trp 128 , i.e. Leu 122 , and Ile 132 (37,38). The mutation of Ile 132 to Met should lead to the disappearance of the resonance at Ϫ0.603 ppm, which has been previously assigned as ␥CH 2 of Ile 132 .…”

Section: Nmr Studies Of Bi 3ϩ Binding To I132m Htf/2n and Comparison mentioning

confidence: 99%

Competitive Binding of Bismuth to Transferrin and Albumin in Aqueous Solution and in Blood Plasma

Sun

Mason

et al. 2001

Journal of Biological Chemistry

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Section: Nmr Studies Of Bi 3ϩ Binding To I132m Htf/2n and Comparison mentioning

confidence: 99%

Competitive Binding of Bismuth to Transferrin and Albumin in Aqueous Solution and in Blood Plasma

Sun

Mason

et al. 2001

Journal of Biological Chemistry

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“…3) suggeststhatthenatureofthefirstkineticphaseofthereaction between Yb 3+ and apo-Tf is the same as that of the reaction between Yb 3+ and Fe C -Tf. Therefore the rapid kinetic phase should correspond to the binding of the metal to the N-lobe, although the binding favors the C-lobe thermodynamically as judged by 1 [29,30,32]. The changes in shifts induced by progressive addition of Lu 3+ (and Yb 3+ ) may be due to the conformational change induced by metal ions, a common feature that was observed previously [16,29,30,32].…”

Section: Discussionmentioning

confidence: 86%

“…The resonance appeared in the high-field region (+0.5 to )1.0 p.p.m., Fig. 5A) was attributed to the methyl groups close to the surface of the aromatic rings of Phe, Trp and Tyr residues due to the ring current effects [29]. Signal b ()0.33 p.p.m) was related to the resonance of the CH 3 group of Leu122, which lies directly above the face of Trp128 [29][30][31].…”

Section: H Nmr Studiesmentioning

confidence: 99%

“…5A) was attributed to the methyl groups close to the surface of the aromatic rings of Phe, Trp and Tyr residues due to the ring current effects [29]. Signal b ()0.33 p.p.m) was related to the resonance of the CH 3 group of Leu122, which lies directly above the face of Trp128 [29][30][31]. Signals g and h were assigned to Leu122 and Val246, respectively; other signals were assigned to methyl groups in the C-lobe [29].…”

Section: H Nmr Studiesmentioning

confidence: 99%

“…Signal b ()0.33 p.p.m) was related to the resonance of the CH 3 group of Leu122, which lies directly above the face of Trp128 [29][30][31]. Signals g and h were assigned to Leu122 and Val246, respectively; other signals were assigned to methyl groups in the C-lobe [29]. Following the addition of 1 mol equiv of Lu 3+ , signal c disappeared, signal d increased in intensity, while signal j decreased, and signal i shifted to the lower frequency.…”

Section: H Nmr Studiesmentioning

confidence: 99%

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Complexation of ytterbium to human transferrin and its uptake by K562 cells

Zhang

Liu

et al. 2002

European Journal of Biochemistry

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There is an increasing interest in the use of lanthanides in medicine. However, the mechanism of their accumulation in cells is not well understood. Lanthanide cations are similar to ferric ions with regard to transferrin binding, suggesting transferrin-receptor mediated transport is possible; however, this has not yet been confirmed. In order to clarify this mechanism, we investigated the binding of Yb 3+ to apotransferrin by UV-Vis spectroscopy and stopped-flow spectrophotometry, and found that Yb 3+ binds to apotransferrin at the specific iron sites in the presence of bicarbonate. The apparent binding constants of these sites showed that the affinity of Yb 3+ is lower than that of Fe 3+ and binding of Yb 3+ in the N-lobe is kinetically favored while the C-lobe is thermodynamically favored. The first Yb 3+ bound to the C-lobe quantitatively with a Yb/ apotransferrin molar ratio of < 1, whereas the binding to the other site is weaker and approaches completeness by a higher molar ratio only. As demonstrated by 1 H NMR spectra, Yb 3+ binding disturbed the conformation of apotransferrin in a manner similar to Fe 3+ . Flow cytometric studies on the uptake of fluorescein isothiocyanate labeled Yb 3+ -bound transferrin species by K562 cells showed that they bind to the cell receptors. Laser scanning confocal microscopic studies with fluorescein isothiocyanate labeled Yb 3+ -bound transferrin and propidium iodide labeled DNA and RNA in cells indicated that the Yb 3+ entered the cells. The Yb 3+ -transferrin complex inhibited the uptake of the fluorescein labeled ferric-saturated transferrin (Fe 2 -transferrin) complex into K562 cells. The results demonstrate that the complex of Yb 3+ -transferrin complex was recognized by the transferrin receptor and that the transferrin-receptor-mediated mechanism is a possible pathway for Yb 3+ accumulation in cells.Keywords: K562 cells; recognition; transferrin; ytterbium.Lanthanides have been suggested for the treatment of a series of diseases and for diagnosis by magnetic resonance imaging [1,2]. Recent studies also show that they could act as scavengers of free radicals [3] and therefore protect cells and tissues from oxidative stress-induced injury. Some lanthanides nuclides were also suggested for palliative therapy. 169 Yb (c-emission, t ½ % 32 days) was reported to provide comparable tumor control and has been considered as a potential replacement for 125 I and 103 Pd in permanent implants [4,5]. Evidently, the intracellular accumulation is very important in these cases, but its mechanism still remains unclear.It was suggested that the particulate-and protein-bound Ln enters the cells by endocytosis [6]; the anionic lowmolecular-mass complexes, via anion channels [7], whereas free Ln 3+ is transported by ionophores [8], Na + /Ca 2+ exchange [9] and self-facilitated diffusion [10]. It is known that Ln 3+ is mainly bound to proteins in the extracellular media (e.g. plasma). Various studies have demonstrated that considerable amounts of Ln are bound to the iron transport prote...

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Transferrins

Luchinat¹,

Sola²

2007

Encyclopedia of Magnetic Resonance

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Uptake of Al3+ into the N-lobe of human serum transferrin

Cited by 36 publications

References 17 publications

Competitive Binding of Bismuth to Transferrin and Albumin in Aqueous Solution and in Blood Plasma

Competitive Binding of Bismuth to Transferrin and Albumin in Aqueous Solution and in Blood Plasma

Complexation of ytterbium to human transferrin and its uptake by K562 cells

Transferrins

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