Interactions of Bismuth Complexes with Metallothionein(II)

Abstract

. Metallothionein (MT)1 is an intriguing, low molecular mass (ϳ7 kDa), cysteine-and metal-rich protein. It was first isolated from equine renal cortex 40 years ago (1) and contains 61 amino acids, of which 20 are cysteine residues. Since then, similar proteins have been isolated from the kidney, liver, and intestines of a variety of animal species (2), fungi (3, 4), plants (5), and metal-resistant bacteria (6 -8). The two major isoforms of mammalian MT (MT(I) and MT(II)) differ only in minor sequence changes and overall charge. Recently, the discovery of a growth inhibitory factor (GIF) from human brain tissue and nerve and its characterization as a metallothionein (MT-III) has stimulated new interests in studying this small protein (9, 10).The functions of metallothionein are still not fully understood. It appears to play a fundamental role in the metabolism of copper and zinc ions under various physiological conditions (11, 12), including its ability to donate metal ions to apo-Zn 2ϩ enzymes (13,14 (18,19), thereby preventing reactions with other cellular targets in mammals and other higher organisms (20). Metallothionein also appears to play a role in radical scavenging, stress response, and the pharmacology of metallodrugs and alkylating agents (12,21,22).The best characterized mammalian metallothioneins contain a single polypeptide chain with seven bound metal ions (either Zn 2ϩ or Cd 2ϩ ). The x-ray crystal structure of rat liver Zn 2 Cd 5 -MT(II) (23) and NMR solution structures of rabbit liver Cd 7 -MT(II) (24), rat liver Cd 7 -MT(II) (25), and human liver Cd 7 -MT (26) show that metallothionein contains two structurally independent ␣ (C-terminal) and ␤ (N-terminal) domains, which are linked in the protein via two amino acids. The seven metal ions are present in clusters of four and three metals bound to bridging and terminal cysteine thiolate ligands, with metal-tothiolate ratios of M 4 S 11 and M 3 S 9 for the ␣-and ␤-domains, respectively (23). When both Zn 2ϩ and Cd 2ϩ are present, Cd 2ϩ binds preferentially to the ␣-domain, whereas Zn 2ϩ is found preferentially in the ␤-domain (23, 28). A Zn 2 Cd three-metal cluster (␤ domain) in MT has the same structure as a Cd 3 cluster (23). The ␣-domain binds Cd 2ϩ ions cooperatively (29). All 20-cysteine residues participate in metal binding, and each of the seven Zn 2ϩ or Cd 2ϩ ions is tetrahedrally coordinated to four cysteine thiolate sulfur atoms (30,31).Bismuth is known to induce the synthesis of renal metallothionein (32), and it has been shown that pretreatment with bismuth complexes can prevent the toxic side effects of the anti-cancer drug cisplatin without compromising its anti-tumor activity (33)(34)(35)(36)

Surfactant‐Directed Synthesis of Branched Bismuth Telluride/Sulfide Core/Shell Nanorods

“…The Bi 4f band at 158 eV corresponds to (Bi 2 Te 2 S) x (Bi 2 S 3 ) 1-x , consistent with the phases identified by X-ray diffraction (XRD), and is supported by the presence of a Te 3d state at 572.2 eV (see Fig. 3e) complexes formed via thioligation, [25] consistent with the color change and the core-level band positions of sulfur and bismuth described above. Because LGTA is not known to form micelle-like templates, the underpinning for nanorod growth along h001i is most likely provided by the organization of…”

A Histidine-rich and Cysteine-rich Metal-binding Domain at the C Terminus of Heat Shock Protein A from Helicobacter pylori

“…Similarly, titration of Bi 3ϩ led to two new bands at ϳ262 and 364 nm in the UV-visible difference spectra (Fig. 2B), which is characteristic for binding of bismuth to cysteine residues (34 To investigate whether metal binding to the protein is reversible, we monitored the intensities of the absorption bands (316 and 364 nm for Ni 2ϩ and Bi 3ϩ , respectively) upon altering the pH of metal-saturated HspA solution. The absorbance was normalized to the percentages of bound metal.…”

“…Previously, we characterized the structure of CBS, the recognition of Bi 3ϩ by the iron and zinc storage proteins, and recently the histidine-rich protein Hpn (20,34,(51)(52)(53). Using a metalloproteomic approach, we screened both Ni 2ϩ -and Bi 3ϩ -binding proteins in H. pylori.…”

A Novel Water‐Soluble Hexanuclear Bismuth Oxido Cluster – Synthesis, Structure and Complexation with Polyacrylate

“…[12,13] In addition to our reports on different bismuth oxido clusters with up to 22 bismuth atoms formed by partial hydrolysis of bismuth(III) silanolates, other large bismuth oxido clusters with up to 38 bismuth atoms have been reported by the groups of Andrews and Dikarev. [12,14] Additional examples of bismuth oxido clusters include the triflate [Bi 9 O 8 (OH) 6 (CF 3 SO 3 ) 5 ], [15] the phosphonate [(tBuPO 3 ) 10 12 ]. [17] The majority of these compounds have low solubility, are sensitive towards water, or are accessible only with low yield.…”

“…[6] In cosmetics, BiOCl is used to give a pearlescent effect. In addition to their almost non-toxic behavior, bismuth-containing materials show high radiopacity, and thus some of them are investigated as potential X-ray imaging agents for computed tomography (CT) and as X-ray contrast additives in bone and dental cements, for example, to enable postoperative examination of their anchorage, texture, and form fit.…”