Heme proteins de novo design

Physical/Electrochemical Studies of de Novo Designed Heme Proteins... 

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. 

Albrecht, T., Li, W.W., Ulstrup, J., Haehnel, W., and Hildebrandt P. (2005) Electrochemical and spectroscopic investigations of immobilized de novo designed heme proteins on metal electrodes. ChemPhysChem, 6, 961-970. 

Gibney, B. R., and Dutton, P. L, 1999, Histidine Placement in De Novo Designed Heme Proteins. Protein Science 8, 1888-1898. 

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. 

Shifman JM, Gibney BR, Sharp RE et al (2000) Heme redox potential control in de novo designed four-a-helix bundle proteins. Biochemistry 39 14813-14821... 

Introducing Heme into De Novo Designed Proteins... 

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