Metalloproteins cysteine

Thiolates (RS ) represent an extensive family of ligands, and include chelating forms. Thiolates are known to act as monodentate donors, but often act in a bridging role. There is a clear biological interest, through participation of thiolates (cysteine residues) as donors in many metalloproteins both as terminal S donors and bridging ligands in, for example, Fe S clusters. 

Chapter 6). Other iron-sulfur proteins, so named because they contain iron sulfur clusters of various sizes, include the rubredoxins and ferredoxins. Rubredoxins are found in anaerobic bacteria and contain iron ligated to four cysteine sulfurs. Ferredoxins are found in plant chloroplasts and mammalian tissue and contain spin-coupled [2Fe-2S] clusters. Cytochromes comprise several large classes of electron transfer metalloproteins widespread in nature. At least four cytochromes are involved in the mitrochondrial electron transfer chain, which reduces oxygen to water according to equation 1.29. Further discussion of these proteins can be found in Chapters 6 and 7 of reference 13. 

Metallothionein was first discovered in 1957 as a cadmium-binding cysteine-rich protein (481). Since then the metallothionein proteins (MTs) have become a superfamily characterized as low molecular weight (6-7 kDa) and cysteine rich (20 residues) polypeptides. Mammalian MTs can be divided into three subgroups, MT-I, MT-II, and MT-III (482, 483, 491). The biological functions of MTs include the sequestration and dispersal of metal ions, primarily in zinc and copper homeostasis, and regulation of the biosynthesis and activity of zinc metalloproteins. 

One ionic bond that often helps establish tertiary structure is a disulfide bond between two cysteine side chain groups—for instance, in the enzyme lysozyme as shown in Figure 2.10. Lysozyme is not a metalloprotein, such as will be studied in this text, but it is a small enzyme and is illustrative of some secondary and tertiary structures found in the more complex molecules described in the following chapters. Lysozyme protects biological species from... 

As with any metalloprotein, the chemical and physical properties of the metal ion in cytochromes are determined by the both the primary and secondary coordination spheres (58-60). The primary coordination sphere has two components, the heme macrocycle and the axial ligands, which directly affect the bound metal ion. The pyrrole nitrogen donors of the heme macrocycle that are influenced by the substitutents on the heme periphery establish the base heme properties. These properties are directly modulated by the number and type of axial ligands derived from the protein amino acids. Typical heme proteins utilize histidine, methionine, tyrosinate, and cysteinate ligands to affect five or six coordination at the metal center. 

Another type of cysteine-containing metalloprotein which has M-S(cys) bonding at the active site is present in electron transfer proteins or metalloenzymes. Sulfur coordination is an important feature, and the covalency and soft environment are possible prerequisites for efficient electron transfer leading to redox catalysis. A distortion at the metal site is induced by the peptide ligands and is a significant feature of the active sites in metalloproteins containing transition metals Fe, Cu, Ni, Mo, etc. 

It is hoped that this chapter will serve to summarize the synthetic methods and structural patterns that underlie this relatively new facet of coordination chemistry and will stimulate further research in this interesting area. The ability of sterically hindered thiols to generate mononuclear species with unusual geometries and oxidation states has arguable relevance to the metal sites found in metalloproteins with cysteine coordination, and this theme will doubtless be pursued further. There appears to be little doubt that whatever the impetus for the chemistry, many new and interestingly reactive complexes will emerge, and that some of these will be capable of interacting with small molecules and will be active for a variety of catalytic and stoichiometric transformations. 

Covalent attachment has also been exploited for protein incorporation of non-native redox active cofactors. A photosensitive rhodium complex has been covalently attached to a cysteine near the heme of cytochrome c (67). The heme of these cytochrome c bioconjugates was photoreducible, which makes it possible for these artificial proteins to be potentially useful in electronic devices. The covalent anchoring, via a disulfide bond, of a redox active ferrocene cofactor has been demonstrated in the protein azurin (68). Not only did conjugation to the protein provide the cofactor with increased water stability and solubility, but it also provided, by means of mutagenesis, a means of tuning the reduction potential of the cofactor. The protein-aided transition of organometallic species into aqueous solution via increased solubility, stability and tuning are important benefits to the construction of artificial metalloproteins. 

Cadmium metallothionein has also been studied extensively. This metalloprotein is high in the amino acid cysteine ( 30%) and is devoid of aromatic amino acids. Metallothionein itself may function to help detoxify cadmium. For some experimental tumors, cadmium appears to be anticarcinogenic (e.g., it reduces the induction of tumors). 

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