A huge number of functions and reactions can be performed by proteins merely based on their amino acids and their spatial arrangement which results in a specific geometric and electronic environment. The diversity and efficiency of functions, however, can be increased by protein-bound cofactors which fulfil their task in close interaction with the surrounding amino acid side chains. Among these cofactors, metals play an important role. They can be bound to proteins directly via specific amino acids such as cysteine and histidine, for example in zinc finger proteins or in iron sulfur cluster proteins. Another possibility is their integration into the 3D-structure of a protein via a prosthetic group. Porphyrine or porphyrine-like molecules with copper or iron as central bound metal ions constitute important structures in this respect. The complexed metal ions are involved in different functions such as mere ligand binding, electron transport or enzyme catalytic reactions. Cytochromes are obviously the most prominent proteins among this group of metallo-enzymes and fulfil important tasks within the cell such as components of the respiratory chain and the photosynthetic apparatus and also as enzymes, the cytochromes P450, which perform a huge number of different oxidation reactions with thousands of substrates. The functional diversity of cytochromes indicates that under the term ‘cytochromes’ different types of hemecontaining proteins are summarized. Besides large differences in the protein structures, a distinction can be made with respect to the coordination of the heme iron. In merely electron transferring cytochromes one ligand for the central iron is the imidazol nitrogen of a histidine residue. In contrast, the cysteine thiol group forms the corresponding ligand in cytochromes P450 and some related enzymes, therefore called heme-thiolate proteins for distinction. These structural features have an impact of the spectroscopic properties of the cytochrome types. As a functional respiratory chain is highly essential for each cell, a functional photosynthesis machine is required in plants, in addition. Probably for this reason, components of these sensitive systems are evolutionary highly conserved. It is noted that based on amino acid and DNA base sequences cytochrome c is for a long time used as a protein to trace phylogenetic and evolutionary relationships between species and higher order taxa. Cytochrome c is the smallest and simplest of the cytochromes of the respiratory chain and due to the fact that it is soluble and easy to handle, it became a model system, often studied with respect to multiple aspects covering evolutionary biology, protein structure, protein biogenesis, biophysics and physiology. These are summarized by Julie Stevens who also focuses on the post-translational maturation of the protein (DOI: 10.1039/c0mt00089b). The buildup of working electron transport chains does not only require the concerted biosynthesis and correct assembly of the involved multi-protein complexes and even supramolecular structures but also of the single holo-proteins such as cytochromes and iron sulfur cluster proteins. Correspondingly, three papers of the Themed Issue deal with specific aspects of cytochrome c biosynthesis. Achievement of the correct three-dimensional structure as well as the proper insertion and covalent attachment of the porphyrine ring system are important for the function of cytochrome c. During protein folding different intermediate stages such as molten and pre-molten globules can be distinguished. This aspect is addressed by the contribution of Ahmad et al. who also consider factors which can influence the structure and function of these states (DOI: 10.1039/c0mt00078g). The supply of heme to apo-cytochrome c is facilitated by the chaperone CcmE. Heme moieties loaded with several metals such as zinc and tin aside from iron show low or no affinity to the chaperone. In the case of Co the heme is reversibly bound to cytochrome c and not attached covalently. Ferguson et al. investigated the reasons for the different chemical behaviour of the metal–heme complexes (DOI: 10.1039/c0mt00085j). For the covalent attachment of iron loaded heme to cytochrome c specific enzymes and specific structural features are required such as the CXXCH binding motif. Alterations of the amino acid sequence of the binding motif or of adjacent areas in connection with the several involved enzyme systems give insight into the requirements for proper and efficient heme attachment (Kleingardner and Bren, DOI: 10.1039/c0mt00086h). The correct spatial positioning and orientation of the heme iron within the protein as well as the surface properties of cytochrome c play an important role as they define the interactions with the redox partners such as cytochrome aa3. Bertini et al. identified three major configuration states of cytochrome which are important for the relevant a Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystr. 67, 44139 Dortmund, Germany b BAM Federal Institute for Materials Research and Testing, Richard Willstaetter-Str. 11, 12489, Berlin, Germany Metallomics Dynamic Article Links
Read full abstract
Mar 18, 2013
Sikan Peng + 7
Open Access