4 results on '"WEIQING ZHONG"'
Search Results
2. Unusual features for zirconium(IV) binding to human serum transferrin
- Author
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Peter J. Sadler, Maolin Guo, Weiqing Zhong, and John Parkinson
- Subjects
Protein Conformation ,Bicarbonate ,Inorganic chemistry ,Kinetics ,chemistry.chemical_element ,Ligands ,Binding, Competitive ,Ferric Compounds ,Biochemistry ,Medicinal chemistry ,Inorganic Chemistry ,chemistry.chemical_compound ,Spectrophotometry ,medicine ,Humans ,Binding site ,Nuclear Magnetic Resonance, Biomolecular ,chemistry.chemical_classification ,HEPES ,Zirconium ,Binding Sites ,medicine.diagnostic_test ,Spectrophotometry, Atomic ,Transferrin ,Carbon-13 NMR ,Recombinant Proteins ,chemistry ,Spectrophotometry, Ultraviolet - 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).
- Published
- 2002
3. Histidine pKa values for the N-lobe of human transferrin: effect of substitution of binding site Asp by Ser (D63S)
- Author
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Gina Kubal, Peter J. Sadler, Weiqing Zhong, Julia M. Goodfellow, David Houldershaw, and Emma Beatty
- Subjects
Models, Molecular ,chemistry.chemical_classification ,Oxalates ,Binding Sites ,Protein Conformation ,Chemistry ,Stereochemistry ,Mutant ,Transferrin ,Hydrogen-Ion Concentration ,Ligand (biochemistry) ,Biochemistry ,Binding constant ,Inorganic Chemistry ,Serine ,Kinetics ,Residue (chemistry) ,Amino Acid Substitution ,Mutagenesis, Site-Directed ,Humans ,Histidine ,Binding site ,Nuclear Magnetic Resonance, Biomolecular - Abstract
The p K a values have been determined for eight of the nine histidine residues and the amino terminus of the N-lobe of human apo-transferrin (hTF/2N), and for seven of the nine histidine residues and the amino terminus of the protein Asp63Ser hTF/2N containing a mutation of the Fe 3+ -ligand Asp63 to Ser63. Calculations suggested that substitution of aspartate by serine would result in decreases of the p K a values of most of the histidine residues in the protein. This was found to be the case experimentally, and allowed assignment of the eCH resonance of His249. For the wild-type protein, the His residue with a p K a of 7.40 was assigned as His249, whereas for the mutant, no observable His residue had a p K a value higher than 6.9. The protonated form of His249 appears to be stabilised by interactions with Asp63, and the high p K a value may be critical for ensuring the release of iron at endosomal pH (5.5). The mutation lowered the apparent binding constant of hTF/2N for the synergistic anion oxalate from log K 4.0 to log K 3.3. 1 H NMR spectral changes induced by Ga 3+ binding to the mutant are compared to those observed for the wild-type protein.
- Published
- 2002
4. Reaction of a platinum(IV) complex with native Cd, Zn-metallothionein in vitro
- Author
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Sheng Yue, Qi Zhang, Baolin Zhang, Yuan Yan, Wenxia Tang, and Weiqing Zhong
- Subjects
Circular dichroism ,Ultraviolet Rays ,Stereochemistry ,chemistry.chemical_element ,Platinum Compounds ,Biochemistry ,Medicinal chemistry ,Redox ,Inorganic Chemistry ,chemistry.chemical_compound ,Animals ,Binding site ,Platinum ,Substitution reaction ,Binding Sites ,Circular Dichroism ,Spectrum Analysis ,Intermolecular force ,Zinc ,Monomer ,chemistry ,Intramolecular force ,Metallothionein ,Rabbits ,Oxidation-Reduction ,Cadmium ,Chromatography, Liquid - Abstract
The first observation of a redox process following a substitution reaction between a platinum(IV) complex K2PtCl6 with rabbit liver native Cd,Zn-MT is presented. The reaction features and products are studied by UV-visible and circular dichroism spectroscopy, chromatography, and X-ray photoelectron spectroscopic measurements. It is a significant complicated reaction comprising redox and substitution reactions. The reaction generates monomeric and dimeric products, and higher oligomers precipitate with intra- or intra- and intermolecular CyS-SCy linkages. Pt(IV) is reduced to Pt(II), which then binds to the monomeric and dimeric products, and may also bind to higher oligomers. The beta-cluster is more reactive than the alpha-cluster, and reacts first with K2PtCl6. Cd5Pt2 and Cd4Pt4 were found when native Cd,Zn-MT reacted with 2 and 4 molar equivalents of Pt(IV) for 2 h in which four Cd ions were located in the alpha-cluster. The amounts of Cd and Pt ions decreased in both monomeric and dimeric products when the reaction was prolonged and intramolecular CyS-SCy linkages increased. Besides the oligomers which precipitated, only dimeric products were formed when the reaction molar ratio of Pt(IV) to MT was more than 10:1. Cd3Pt6 and Cd1Pt8 were obtained when the reaction occurred for 2 and 72 h, respectively. The structure of the clusters may exist when native Cd, Zn-MT reacts with substoichiometric quantities of K2PtCl6 (0.5 K2PtCl6 per MT thiolate) for a short time (2 h), but may be partly disrupted with stoichiometric or excess quantities of K2PtCl6 (or = 0.5 K2PtCl6 per MT thiolate) for a long time. The disruption of the cluster structures results in an increase of the nonbridge thiolate and an increase of the binding sites to Pt ions. The mechanism of the antitumor activity and developing drug resistance of Pt(IV) complex drugs is discussed.
- Published
- 1997
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