Equilibrium constants for the binding of aluminum to human serum transferrin

Abstract

believe that the precise definition of the coordinate geometry of copper a t the active site will be crucial to understanding its functional operation. Also, the subtle changes t h a t allow t h e dinuclear site to become catalytically active in, for example, tyrosinase and laccase'1*42-44 will also be an interesting outcome of gaining a more precise definition of t h e active-site structure of hemocyanin a n d its related binuclear copper proteins.45 42)Karlin, K. D.; Gultneh, Y. Prog. Inorg. Chem. 1987, 35, 219. 43) Latour, J.-M. Bull. SOC. Chim. Fr. 1988, 508. 44) Sorrell, T. N. Tetrahedron 1989, 45, 3. 45) The structure of the multicopper-containing enzyme ascorbate oxidase has just appeared: Messerschmidt, A.; Rmi, A.; Ladenstein, R.; Huber, R.; Bolognesi, M.; Gatti, G.; Marchesini; Petruzzelli, R.; Finazzi-Agrb, A. J . Mol. Biol. 1989, 206, 513. 124021-05-2; 5, 124021-07-4; [ C U ( M~C N )~] C F~S O , , 58452-28-1; [Cu-(MeCN)4]C104, 14057-91-1; [Cu( MeCN),]BF4, 1541 8-29-8. Supplementary Material Available:Tables S1, S4, S7, and SI0 (anisotropic thermal parameters), Tables S2, S5, S8, and SI 1 (bond distances), and Tables S3, S6, S9, and S12 (bond angles) for compounds 1-4, respectively (15 pages). Ordering information is given on any current masthead page.The binding of aluminum to human serum transferrin in 0. IO M N-(2-hydroxyethyl)piperazine-N'-ethanesulfonic acid and 5 mM sodium bicarbonate at pH 7.4 has been studied by difference ultraviolet spectrophotometry. Aluminum binding produces peaks at 240 and 288 nm that are characteristic of binding at the transferrin specific metal binding sites. The more intense peak at 240 nm has a molar absorptivity of 14 800 f 1600 M-' cm-l and has been used to determine two macroscopic aluminum binding constants of log KI* = 13.5 & 0.2 and log K2* = 12.5 f 0.3. Titrations of both forms of monoferric transferrin with AI3+ indicate that the larger K I * value is associated primarily with AI binding at the C-terminal site and the smaller K2* value is associated primarily with the N-terminal site. The AI-transferrin binding constants have been used to include transferrin in the equilibrium distribution of aluminum calculated by using a computer model of serum. This model has been used to evaluate the potential of several low molecular weight ligands for use in decorporation of aluminum. Sciences Research Support Grant No. 2S07RR07170-11 at the University of Idaho. We wish to thank Dr. A. E. Martell for helpful discussions and for providing preprints of ref 37 and 54.Registry No. EXAFS spectroscopy has been applied to investigate the nature and the stereochemistry of the iron(II1) binding sites in the protein phosvitin from chicken eggs in water solution with an iron/protein molar ratio of 10/1 at pH 7.2. The main result is that the iron atoms are bound to the protein in an octahedral environment and that the main binding sites are provided by the oxygen atoms of serine-bound phosphate groups at 1.93 (2) A from the metal. The average number of bound phosphate groups is 4.4...

Rationalization of the Strength of Metal Binding to Human Serum Transferrin

“…The difference in binding constants, logKT-logK: = 1.3, is greater than would be the case if both lobes bound Sc3+ equally strongly (dlogK* = 0.6). Therefore, it can be concluded that one lobe has a higher affinity for Sc3+ than the other, as has been found for several other metallotransferrins [ 10,15,201.…”

“…In particular, tyrosinate side-chains are likely to play dominant roles since two of them bind to the metal and transferrin is the only known metalloprotein in which this is known to be the case. About 30 metal ions are known to bind to transferrin with either carbonate, oxalate or other carboxylates as synergistic anion [3], and the binding constants for 12 divalent and trivalent metal ions with carbonate as anion have previously been determined by ultraviolet difference spectroscopy [8,10,15,[22][23][24][25][26].…”

New Tris(hydroxypyridinones) as Iron and Aluminium Sequestering Agents: Synthesis, Complexation and In Vivo Studies

“…Therefore, pM values were calculated for the Fe and Al complexes with the ligands under study and are depicted on Table 2, together with the corresponding values for a set of synthetic and biological ligands, namely, polyhydroxypyridinone-based ligands, such as hexadentate 3,2-HP (tripodal Tren(Me-3,2-HOPO) (Tren = tris(2-aminoethyl)amine, Me-3,2-HOPO = 1-methyl-3,2-hydroxypyridinone), [24] linear 3,4-LI(Me-3,2-HOPO) (3,4-LI = N 1 -(3-aminopropyl)butane-1,4-diamine), [25] a hexadentate tripodal 3,4-HP (CP254), [26] tetradentate 3,4-HP (IDAA C H T U N G T R E N N U N G (3,4-HP) 2 (IDA = iminodiacetic acid), [27] EDTAA C H T U N G T R E N N U N G (3,4-HP) 2 [12] ), and some well known non-hydroxypyridinone strong synthetic chelators such as N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED), [28] EDTA, [29] DTPA = diethylene triamine pentaacetic acid, [29] desferrioxamine (DFO), [30,31] DFP, [19] and the endogenous ligand, transferrin. [30,32] Analysis reveals that the herein developed hexadentate chelators are more potent than the others, except HBED, reported in Table 2 towards iron. Thus, the high metal chelating affinity revealed by these novel hexadentate hydroxypyridinones undoubtedly constitutes a strong motivating factor for pursuing biodistribution studies with both ligands to evaluate their removal capacity towards hard metal ions.…”

An in vitro study on the binding of Al(III) to human serum transferrin with the isoelectric focusing technique

“…In a number of publications absorption at 240 nm has been taken to reflect the formation of the AI Tf complex and as such this was used to monitor the binding of Study of Al-Tf bindin9 by IEF aluminum to transferrin (Trapp 1983, Cochran et al 1984, Harris & Sheldon 1990, McGregor et al 1990, Kubal et al 1992, Aramini et al 1993. Based on this assumption, maximal absorption at 240 nm was assumed to be correlated with full saturation.…”

“…Like iron, in the circulation, aluminum is transported by transferrin, while albumin and citrate appear to play a minor role (van Ginkel et al 1990, Harris & Sheldon 1990. Competition between iron and aluminum for transferrin binding is suggested in view of the negative correlation between serum iron and serum aluminum in the dialysis population (Vanuytsel et al 1992, van Landeghem et al 1994.…”