Prosthetic groups in proteins

Classes of metalloproteins. Transition ion prosthetic groups in proteins are... 

Note, however, that the -59In mV change per pH-unit is seldom found for prosthetic groups in proteins because association of protons is usually not directly on the coordination complex (which could result in loss of the metal) but rather on a nearby (or not-so-nearby) amino-acid side chain. So, the change can be anywhere between 0 and -59In mV. This information can be quite valuable for an understanding of the mechanism of action of the metalloprotein, but it does mean that we have to carry out EPR-monitored redox titrations at several different pH-values. 

In spite of the close theoretical relationship between EPR and NMR spectroscopy, EPR has only very narrow applications. The primary reason for this is that the EPR phenomenon is spectroscopically silent unless there are unpaired electrons. Most biological macromolecules are closed shell molecules and contain no unpaired electrons. Therefore, EPR is of little real value for biological macromolecular structure characterisation. The only exception to this rule is that certain prosthetic groups in proteins may contain redox active metal centres/clusters that have transient or even permanent unpaired electrons (see Chapter 4). These metal centres/ clusters can be studied by EPR spectroscopy in order to demonstrate the presence of unpaired electrons. Thereafter, EPR data may then be used to derive the relative structural arrangements of metals within centres or clusters, and to assign putative distributions of redox states should there be any obvious redox heterogeneity. EPR is also useful to detect transient or even metastable radical formation during bio catalysis (see Chapter 8). 

Heme A molecule consisting of a porphyrin ring (either protoporphyrin IX or a derivative) with a central complexed iron it serves as a prosthetic group in proteins such as myoglobin, hemoglobin, and cytochromes. 

The presence of a cofactor or a prosthetic group in protein structure, by helping the folding process and stabilizing the structure, represents a particular case (this point is discussed in detail in Chapter 11). 

Covalently Bound Flavins. The FAD prosthetic group in mammalian succinate dehydrogenase was found to be covalently affixed to protein at the 8 a-position through the linkage of 3-position of histidine (102,103). Since then, several covalently bound riboflavins (104,105) have been found successively from the en2ymes Hsted in Table 3. The biosynthetic mechanism, however, has not been clarified. 

Casein may be considered to be a conjugated protein, that is the protein is associated in nature with certain non-protein matter known as prosthetic groups. In the case of casein the prosthetic group is phosphoric acid. The protein molecule is also associated in some way with calcium. The presence of these inorganic materials has an important bearing on the processability and subsequent use of casein polymers. 

The spectral properties of four major phycobiliproteins used as fluorescent labels can be found in Tables 9.1 and 9.2. The bilin content of these proteins ranges from a low of four prosthetic groups in C-phycocyanin to the 34 groups of B- and R-phycoerythrin. Phycoerythrin derivatives, therefore, can be used to create the most intensely fluorescent probes possible using these proteins. The fluorescent yield of the most luminescent phycobiliprotein molecule is equivalent to about 30 fluoresceins or 100 rhodamine molecules. Streptavidin-phycoerythrin conjugates, for example, have been used to detect as little as 100 biotinylated antibodies bound to receptor proteins per cell (Zola et al., 1990). 

Iron-sulfur clusters (7) occur as prosthetic groups in oxidoreductases, but they are also found in lyases—e.g., aconitase (see p. 136) and other enzymes. Iron-sulfur clusters consist of 2-4 iron ions that are coordinated with cysteine residues of the protein (-SR) and with anorganic sulfide ions (S). Structures of this type are only stable in the interior of proteins. Depending on the number of iron and sulfide ions, distinctions are made between [Fe2S2], [Fe3S4], and [Fe4S4] clusters. These structures are particularly numerous in the respiratory chain (see p. 140), and they are found in all complexes except complex IV. 

Porterfield. W. W., 295 Positive oxidation states, halogens in, 837-848 Posttransition metals, 28. 876 Potassium, 309, 582-587 Potentials, electrode, 378-383 Pourbaix diagram, 591-592 Praseo complex, 388,491, 493 Predominance area diagram, 591 Prewitt, C. T., 116-117 Principal axis, 51 Prism, trigonal prism, 489-491 Probability function, 13 Prosthetic group, 919 Proteins, and blue copper proteins, 912-916 Proton... 

An iron porphyrin is the prosthetic group in the oxygen transport and storage proteins, hemoglobin and myoglobin. Consequently there has been much interest in porphyrin complexes, especially of first row transition metals, as model systems for oxygen transport and storage. Much interest has also been shown in metal porphyrins as models for oxidases, in particular cytochrome P-450. 

These are rarely found free but occur as a common prosthetic group of proteins. The first such protein to be extensively studied was the iron porphyrin (Greek porphyra, purple) haemoglobin. This and other iron-porphyrin proteins play a vital role in the physiological activity of nearly all forms of life.146 These forms have the same basic structure (39) but differ in the nature of the pyrrole substituents these are shown for the major porphyrins in Table 13. It has become common practice to refer to all the iron-porphyrin proteins as haem proteins. The function of haemoglobin is, of... 

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