Metal-thiolate clusters

Biomimics of noncatalytic, or structural, zinc generally focus on zinc-thiolate clusters designed after the metal—thiolate clusters of metal-lothionein (see Section IV,C). Adamantoid anions of formula [ (jiz-SPh)6(ZnSPh)4] are targets of synthetic and structural study, where each metal ion is coordinated in tetrahedral fashion by bridging and terminal thiolate ligands (see Hencher et al., 1985 Dean and Vittal, 1987, and references cited therein). 

Fig. 39. The three-metal-thiolate cluster in the j8-domain of rat liver metallothionein II (C. D. Stout, personal communication).

Several studies on models have been reported, both on the binding of a range of metals to apometallothionein and the design of ligands, particularly with Cys-X-Cys and Cys-X-Y-Cys arrangements as found for metallothionein.1163,1164 All metal derivatives appear to bind in metal-thiolate clusters.1149 Platinum has also been found bound to metallothionein in rat tissues following treatment with cisplatin and the trans isomer.1165... 

Figure 3 Schematic drawing of the two metal-thiolate clusters in mammalian Zn2,Cd5-MT-2 A Cd4Cysn cluster in the C-terminal a domain and a Zn2CdCys9 cluster in the N-terminal /3 domain. atoms are labeled by Cys residue number (4mt2)...

At present, our knowledge about the structure of the Cu -containing manunahan MT-1 and MT-2 isoforms is limited to the fact that fully Cu-loaded MT form contains 12 Cu ions organized in two metal-thiolate clusters, where, in contrast to divalent metal ions, the monovalent copper ions are coordinated by two or three cysteine ligands (see Copper Inorganic Coordination Chemistry)... 

Apart from the conformational flexibility of the polypeptide chain, dynamic processes within the metal-thiolate clusters have also been recognized. Thus, in the Zn K-edge EXAFS studies of Zn7-MT, substantial movements within the cluster are believed to preclude the observation of Zn-Zn backscattering (second shell) atroom temperature. Similarly, in the PAC spectra of " Cd-MT, the damping of the major oscillatory component was attributed to inordinately large charge fluctuations in the irmnediate enviromnent of the " Cdnuclei. ... 

The metal selectivity of metal-thiolate clusters in MT has been examined by offering seven equivalents of two metal ions in different relative proportions to apoMT that is, Co VCd Zn /Cd , Co /Zn and Fe /Cd . Subsequently, the respective metal distributions within the clusters were determined using electronic absorption, MCD, " Cd NMR, Fe Mossbauer and EPR spectroscopy, as required. The results of the cluster forms in mixed-metal MT derivatives are summarized in Table 2. 

R570 M. Vasak, D. W. Hasler and P. Faller, Metal-Thiolate Clusters in Neuronal Growth Inhibitory Factor (GIF) , J. Inorg. Biochem., 2000, 79,7... 

Fig. 12. Proposed structures of metal-thiolate clusters of Cu6- and Cu8-thioneins from yeast. From Hartmann et al. 1992 [66] with permission...

Fig. 6.1 Model of the molecular structure of mammalian metallothionein, showing the primary sequence, and two topologically separate metal-thiolate clusters. (After Otvos and Armitage 1980.)...

---