Proteins zinc-binding

Ippolito, J. A., Baird, T. T., Jr., McGee, S. A., Christianson, D. W., and Fierke, C. A. (1995) Structure-assisted redesign of a protein-zinc-binding site with femtomolar affinity. Proc. 

Lesburg, C. A. and Christianson, D. W., X-ray crystallographic studies of engineered hydrogen bond networks in a protein-zinc binding site, J. Am, Chem. Soc. 117, 6838-6844 (1995). 

Zinc is an essential component of a large number of enzymes. Zinc-containing enzymes are involved in the synthesis and degradation of major metabolites, and serve to regulate the replication, transcription, and translation of genetic material. In some proteins zinc binds with a coordination number of 4 to sulfur and nitrogen, while in others in which it also binds oxygen the coordination number is S or 6. 

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.)...

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

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... 

Elevated metallothionein levels are not necessarily indicative of heavy-metal insult. Starcher et al. (1980) show that liver metallothionein levels in mice are elevated following acute stress or starvation, and that this effect is blocked by actinomycin D, a protein synthesis inhibitor. It is further emphasized that not all zinc-binding proteins are metallothioneins (Webb etal. 1985 ... 

Cows and calves fed low-zinc diets of 25 mg Zn/kg ration showed a decrease in plasma zinc from 1.02 mg/L at start to 0.66 mg/L at day 90 cows fed 65 mg Zn/kg diet had a significantly elevated (1.5 mg Zn/L) plasma zinc level and increased blood urea and plasma proteins (Ram-achandra and Prasad 1989). Biomarkers used to identify zinc deficiency in bovines include zinc concentrations in plasma, unsaturated zinc-binding capacity, ratio of copper to zinc in plasma, and zinc concentrations in other blood factors indirect biomarkers include enzyme activities, red cell uptake, and metallothionein content in plasma and liver (Binnerts 1989). 

Webb, J., D.J. Macey, and V. Talbot. 1985. Identification of ferritin as a major high molecular weight zinc-binding protein in the tropical rock oyster, Saccostrea cuccullata. Arch. Environ. Contam. Toxicol. 14 403-407. 

Jensen, A. A., Sheppard, P. 0., Jensen, L. B., O Hara, P. J., and Brauner-Osbome, H. (2001) Construction of a high affinity zinc binding site in the metabotropic glutamate receptor mGluRl. Noncompetitive antagonism from the amino-terminal domain of a family C G protein-coupled receptor. J. Biol. Chem. 276,10110-10118. 

Alberts, I. L., Nadassy, K., and Wodak, S. J. (1998) Analysis of zinc binding sites in protein crystal structures. Protein. Sci. 7,1700-1716. 

Crystal structures of a histone deacetylase-like protein (HDLP) and HDAC8 have confirmed a general pharmacophore model for HDAC inhibitors, comprising a cap joined by a hydrophobic linker to a zinc-binding group (ZBG). This model is exemplified by SAHA and the natural product HDACi Trichostatin A (TSA) 2. 

Figure 12.1 Zinc-binding sites in enzymes can be catalytic, structural or cocatalytic. The protein ligands are indicated by smaller filled circles. (From Auld, 2001. With kind permission of Springer Science and Business Media.)...

ZnFZZ Zinc-binding domain, present in Dystrophin, CREB-binding protein E(MFP) 2(2) 11(12) ... 

A. Filipek, C. W. Heizmann, and J. Kuznicki, Calcyclin is a calcium and zinc binding protein, FEES Lett. 264, 263-266 (1990). 

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