Heme peptide, structure

The most valuable confirmation of this view to date is, without doubt, to be found in the known structures of homologous proteins and peptide hormones, that is compounds of identical biological function isolated from different species. As is well known, the primary structures of the homologous insulins, corticotropins, hypertensins, posterior pituitary hormones, and heme peptide sequences from cytochromes c are closely similar and differ only at certain definite sites in the peptide chains. These can, in particular, serve as a useful point of departure in a search for more general principles governing protein structure, and in the comparison of different proteins. 

Fig. 8. Internal regularities in the structure of the heme peptide from Chromalium...

An inverse task is given when there is demand for a macromolecule that specifically binds a small ligand. This question has only recently been addressed by peptide chemistry. For example, antiparallel bundles of four a-helices, which were assembled on a cyclic peptide structure as template, have been used to create hydro-phobic cavities for heme as a low-molecular-weight compound [3]. The specific complexation of Fe " protoporphyrin IX was facilitated by the proper positioning of liganding His residues. While this approach could be interesting from the perspective of rational protein design, it may be limited to special applications, and detailed structural information about the complex is not yet available. 

Poulos TL, Finzel BC (1984) Heme enzyme structure and function. In Meant MT (ed) Peptide and protein reviews. Marcel Dekker, New York, pp 115-171... 

Poulos, T. and Finsel, B., Heme enzyme structure and fimction. Peptide Protein Revs., 4,115, 1984. 

Important products derived from amino acids include heme, purines, pyrimidines, hormones, neurotransmitters, and biologically active peptides. In addition, many proteins contain amino acids that have been modified for a specific function such as binding calcium or as intermediates that serve to stabilize proteins—generally structural proteins—by subsequent covalent cross-hnk-ing. The amino acid residues in those proteins serve as precursors for these modified residues. Small peptides or peptide-like molecules not synthesized on ribosomes fulfill specific functions in cells. Histamine plays a central role in many allergic reactions. Neurotransmitters derived from amino acids include y-aminobutyrate, 5-hydroxytryptamine (serotonin), dopamine, norepinephrine, and epinephrine. Many drugs used to treat neurologic and psychiatric conditions affect the metabolism of these neurotransmitters. 

Two dendrimers based on Fe-porphyrin core carrying peptide-like branches of different sizes have been synthesized in order to have more open and a more densely packed (23) structures [43]. The electrochemical behavior has been examined in CH2C12 and in aqueous solution. In the less polar solvent, the two dendrimers show similar potentials for the Fem/Fen couple, suggesting that the iron porphyrins in both the more open and the more densely packed dendrimers experience similar microenvironments. On the contrary, in water the behavior of the two dendrimers is very different since the reduction from Fem to Fe11 is much easier for the densely packed dendrimer. This result can be explained considering that in the dendrimer with the relatively open structure the aqueous solvation of the iron porphyrin is still possible, whereas in the densely packed one the contact between the heme and the external solvent is signifi-... 

While these complex model heme proteins have a large potential for functionalization, an interesting approach that is very different has been taken by other workers in that the heme itself functions as the template in the formation of folded peptides. In these models peptide-peptide interactions are minimized and the driving force for folding appears to be the interactions between porphyrin and the hydrophobic faces of the amphiphiUc peptides. The amino acid sequences are too small to permit peptide-peptide contacts as they are separated by the tetrapyrrole residue. These peptide heme conjugates show well-re-solved NMR spectra and thus well-defined folds and the relationship between structure and function can probably be determined in great detail when functions have been demonstrated [22,23,77]. They are therefore important model systems that complement the more complex proteins described above. 

Since the primary structure of a peptide determines the global fold of any protein, the amino acid sequence of a heme protein not only provides the ligands, but also establishes the heme environmental factors such as solvent and ion accessibility and local dielectric. The prevalent secondary structure element found in heme protein architectures is the a-helix however, it should be noted that p-sheet heme proteins are also known, such as the nitrophorin from Rhodnius prolixus (71) and flavocytochrome cellobiose dehydrogenase from Phanerochaete chrys-osporium (72). However, for the purpose of this review, we focus on the structures of cytochromes 6562 (73) and c (74) shown in Fig. 2, which are four-a-helix bundle protein architectures and lend themselves as resource structures for the development of de novo designs. 

The heme moiety provides de novo designed heme proteins with an intrinsic and spectroscopically rich probe. The interaction of the amide bonds of the peptide or protein with the heme macrocycle provides for an induced circular dichroism spectrum indicative of protein-cofactor interactions. The strong optical properties of the heme macrocycle also make it suitable for resonance Raman spectroscopy. Aside from the heme macrocycle, the encapsulated metal ion itself provides a spectroscopic probe into its electronic structure via EPR spectroscopy and electrochemistry. These spectroscopic and electrochemical tools provide a strong quantitative base for the detailed evaluation of the relative successes of de novo heme proteins. 

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