Zinc binding

An interesting metal-binding motif in proteins is the zinc finger, which is a helix-turn-helix motif that binds a zinc ion via four sulfur atoms of cysteine residues, or via two sulfur and two nitrogen atoms (from histidine). This motif, shown in Fig. 28, was first identified by NMR studies [71], and has now been found in the crystal structures of several protein-nucleic acid complexes [72]. 

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Figure 1.9 Examples of functionally important intrinsic metal atoms in proteins, (a) The di-iron center of the enzyme ribonucleotide reductase. Two iron atoms form a redox center that produces a free radical in a nearby tyrosine side chain. The iron atoms are bridged by a glutamic acid residue and a negatively charged oxygen atom called a p-oxo bridge. The coordination of the iron atoms is completed by histidine, aspartic acid, and glutamic acid side chains as well as water molecules, (b) The catalytically active zinc atom in the enzyme alcohol dehydrogenase. The zinc atom is coordinated to the protein by one histidine and two cysteine side chains. During catalysis zinc binds an alcohol molecule in a suitable position for hydride transfer to the coenzyme moiety, a nicotinamide, [(a) Adapted from P. Nordlund et al., Nature 345 593-598, 1990.)...

Figure 13.23 The F-G loop in the C-terminal domain of the prolactin receptor is involved in a unique interaction, (a) The F-G loop of the growth hormone receptor (blue) is not involved in any specific interactions with the growth hormone (red), (b) The F-G loop in the prolactin receptor forms a strong zinc-binding site that links the receptor (green) to the hormone (red). (Adapted from W. Somers et at.. Nature 372 478-481, 1994.)...

KELL blood group antigen is a plasma membrane protein isolated from red cells homologous to zinc-binding glycoproteins with neutral endopeptidase activity. 

Carbonic anhydrase an insight into the zinc binding site and into the active cavity through metal substitution. I. Bertini, C. Luchinat and A. Scozzafava, Struct. Bonding (Berlin), 1982, 48, 46-92 (296). 

Bertini I, Luchinat C, Scozzafava A (1982) Carbonic Anhydrase An Insight into the Zinc Binding Site and into the Active Cavity Through Metal Substitution. 48 45-91 Bertrand P (1991) Application of Electron Transfer Theories to Biological Systems. 75 1-48 Bill E, see Trautwein AX (1991) 78 1-96 Bino A, see Ardon M (1987) 65 1-28 Blanchard M, see Linares C (1977) 33 179-207 Blasse G, see Powell RC (1980) 42 43-96... 

The general topology of rubredoxins is also observed in the general zinc-ribbon motif in RNA polymerases or in transcription factors (59). The first published zinc-ribbon structure was that of the nucleic-acid binding domain of human transcriptional elongation factor TFIIS (PDB file ITFI) 40). These zinc binding domains and rubredoxins... 

Bertini, /., Luchinat, C., Scozzafava, A. Carbonic Anhydrase An Insight into the Zinc Binding Site and into the Active Cavity Through Metal Substitution. Vol. 48, pp. 45-91. 

Santisteban, I., Arredondo-Vega, F. X., Kelly, S., Debre, M., Fischer, A., Pdrignon, J. L., Hilman, B., Eldahr, J., Dreyfus, D. H., Howell, P. L., and Hershfield, M. S Four new adenosine deaminase mutations, altering a zinc-binding histidine, two conserved alanine, and a 5 splice site. Hum. Mutat. 5,243-250 (1995). 

Bode W, Gomis-Ruth FX, Stocker W. Astacins, serralysins, snake venom and matrix metalloproteinases exhibit idential zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the metzincins. FEBS Lett 1993 331 134-140. 

A number of mixed crown ligands have been synthesized combining N, O, or S ligands. The larger, more flexible, ligand systems can show interesting coordination patterns as the zinc binds to its preferred donor set. 

Bharadwaj synthesized the zinc complex of a mixed donor cryptand (94). The X-ray structure shows that the zinc binds in the tetraamine cavity at the base of the ligand in a tetrahedral environment and not to the oxygen donors. This demonstrates the expansion potential of the cavity compared with the free ligand.740... 

A porphyrin compound with a 2,9-dimethyl- 1,10-phenanthroline functionality fused at the beta-pyrrole positions is a phthalocyanine analog, and formed a complex with zinc in the cavity and a further zinc binding to the phenanthroline group. The absorption and emission spectra of the compound with and without the external zinc demonstrated the strong effects of the second metal binding on the porphyrin 7r-system.840... 

The recruitment of zinc for a structural role, or to activate an enzyme, has been observed. The zinc ion induces the dimerization of human growth hormone (hGH), with two Zn ions associated per dimer of hGH. This is confirmed by replacement of possible zinc binding residues resulting in weakened binding of the zinc ion. Formation of a zinc-hGH dimeric complex may be important for storage of hGH in secretory granules.975 In a toxic role, anthrax lethal factor is one of the three components of the secreted toxin and is a zinc-dependent protease that cleaves a protein kinase and causes lysis of macrophages.976... 

J.S. Valentine, M.W. Pantoliano, PJ. Mcdonnell, A.R. Burger, and S.J. Lippard, pH-dependent migration of copper(II) to the vacant zinc-binding site of zinc-free bovine erythrocyte superoxide dismutase. Proc. Natl. Acad. Sci. U.S.A. 76, 4245-4249 (1979). 

M.W. Pantoliano, P.J. McDonnell, and J.S. Valentine, Reversible loss of metal ions from the zinc binding site of copper-zinc superoxide dismutase. The low pH transition. J. Amer. Chem. Soc. 101, 6454— 6456 (1979). 

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