Peptides metal binding

Dynamic combinatorial libraries (DCLs) are continuously interconverting libraries that evenmally evolve to an equilibrium distribution [61-65]. This approach has been used successfully in the discovery of stable supramolecular assemblies from mixtures. Due to the nearly endless possible peptide sequences that can potentially be synthesised, the DCL approach is attractive for the identification of supramolecular peptide interactions. Indeed, disulfide exchange between cysteine residues has been explored for this purpose [66, 67] as has peptide-metal binding [68]. We have recently demonstrated protease-catalysed amide exchange in this context, which allows for the evolution of the self-assembled peptide structures, and will therefore allow exploration of peptide sequence space for biomaterials design. 

Both plants and yeast are known to produce phytochelatins (PC ), peptide metal-binding ligands, in response to heavy metal (especially Cd2+) toxicity heavy metal ions activate the enzyme, PC synthase (PCS), which produces PC s from glutathione (GSH) see equation (7.1). 

A similar cadmium-binding complex of peptides is produced by the alga Chlorella fusca as well as other Phyto-phyta (Gekeler et al., 1988). Phytochelatins have been identified in the roots of heavy-metal-sensitive Acer pseudoplatanus and resistant Silene cucubalus plants grown in zinc-rich soil, whereas plants grown in the absence of this metal lacked these peptides. Metal-binding phytochelatins appear to be specifically induced in plants in heavy-metal-enriched ecosystems (Grill et al., 1988). 

In addition to being a remarkable demonstration of the power of computer-based combinatorial design of a protein fold, this designed peptide is the shortest known peptide consisting entirely of naturally occurring amino acids that folds into a well-ordered structure without metal binding, oligomerization or disulfide bond formation. 

Grill, E., Winnacker, E.-L. Zenk, M.H. (1987). Phytochelatins, a class of heavy-metal-binding peptides from plants, are functionally analogous to metallo-thioneins. Proceedings of the National Academy of Sciences, USA, 84, 439-43. 

PROTEIN STRUCTURE OF PEPTIDE DEFORMYLASES Three-dimensional Structure Metal-binding Site... 

The energetics of peptide-porphyrin interactions and peptide ligand-metal binding have also been observed in another self-assembly system constructed by Huffman et al. (125). Using monomeric helices binding to iron(III) coproporphyrin I, a fourfold symmetric tetracarboxylate porphyrin, these authors demonstrate a correlation between the hydropho-bicity of the peptide and the affinity for heme as well as the reduction potential of the encapsulated ferric ion, as shown in Fig. 12. These data clearly demonstrate that heme macrocycle-peptide hydrophobic interactions are important for both the stability of ferric heme proteins and the resultant electrochemistry. 

An analysis of metal binding to peptide carbonyl groups (Chakrabarti, 1990), mainly calcium ions in protein crystal structures, shows that the cations tend to lie in the peptide plane near the C=0 bond direction. Generally, this binding occurs in turns in proteins or in regions with no regular secondary structures. Ca---0 distances range from 2.2 to 2.5 A, and metal ions do not deviate by more than 35° from the peptide plane. Thus, metal ions in proteins do not, Chakrabarti observed, bind in lone-pair directions. 

Fig. 41. Berg s proposed structure of a zinc finger peptide (left) hydrogen bond pattern (center) ribbon diagram illustrating secondary-structure components (right) molecular model illustrating conserved metal-binding and hydrophobic residues. [Reprinted with permission from Berg, J. M. (1988) Proc. Natl. Acad. Set. U.S.A. 85, 99-102.]...

The engineering of zinc-binding sites in a-helical peptides, where metal binding stabilizes protein tertiary structure, has been reported by Handel and DeGrado (1990). In these experiments zinc-binding sites are incorporated into a dimeric helix-loop—helix peptide (H3 2) and a protein composed of four helices connected by three short loop sequences (H3 4). a model of one subunit of the H3 2 dimer is found in Fig. 47. In addition to metal complexation by two histidine residues at positions n and n+4 of one a helix, the metal is coordinated by a third histidine residue of an adjacent a helix. The composition of the zinc coordination polyhedron is like that of carbonic anhydrase (i.e., Hiss), and spectroscopic results suggest that all three histidine residues are involved in zinc complexation. This work sets an important foundation... 

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