High-potential iron proteins structure

Page, C. C., Moser, C. C., Chen, X. and Dutton, P. L, 1999, Natural engineering principles of electron tunneling in biological oxidation-reduction. Nature 402, 47 -52. Parisini, E., F. Capozzi, P. Lubini, V. Lamzin, C. Luchinat, and G. M. Sheldrick. 1999. Ab initio solution and refinement of two high potential iron protein structures at atomic resolution. Acta Crystallography D. 55, 1773-1784. 

Nonrepetitive but well-defined structures of this type form many important features of enzyme active sites. In some cases, a particular arrangement of coil structure providing a specific type of functional site recurs in several functionally related proteins. The peptide loop that binds iron-sulfur clusters in both ferredoxin and high potential iron protein is one example. Another is the central loop portion of the E—F hand structure that binds a calcium ion in several calcium-binding proteins, including calmodulin, carp parvalbumin, troponin C, and the intestinal calcium-binding protein. This loop, shown in Figure 6.26, connects two short a-helices. The calcium ion nestles into the pocket formed by this structure. 

Three core oxidation states are known for protein-bound [Fe4-S4(S.Cys)4]3+ clusters as illustrated in Figure 2.9. Native proteins exhibit either the [Fe4-S4]2+ + or the [Fe4-S4]3+,2+ redox couple, with proteins involved in the latter couple being referred to historically as HiPIP (high-potential iron protein). The three oxidation states have not been traversed in one protein unless its tertiary structure is significantly perturbed. 

By any sort of definition, turns are an important feature of protein structure. Kuntz (1972) found 45% of protein backbone in turns or loops Chou and Fasman (1977) found 32% of protein chain in turns (counting four residues per turn) and Zimmerman and Scheraga (1977b) found 24% of the nonhelical residues in turns (counting only the central dipeptide). There are also some particular proteins whose structure appears heavily dependent on turns Fig. 38 shows high-potential iron protein (Carter et ah, 1974), with the 17 turns in 85 residues indicated and their location at the surface evident. 

Fig. 105. Examples of small disulfide-rich or metal-rich proteins (shown on the right side) compared with their more regular counterparts in other structural categories (shown at the left), (a) Tobacco mosaic virus protein, an up-and-down helix bundle (b) cytochrome bs, a distorted up-and-down helix bundle (c) trypsin domain 1, a Greek key antiparallel /3 barrel (d) high-potential iron protein, a distorted Greek key /3 barrel (e) glutathione reductase domain 3, an open-face sandwich fi sheet (f) ferredoxin, a distorted open-face sandwich f) sheet.

Freer, S. T., Alden, R. A., Carter, C. W., Jr., and Kraut, J. (1975). Crystallographic structure refinement of Chromatium high potential iron protein at two angstroms resolution. /. Biol. Chem. 250, 46-54. 

The multinuclear tetrahedral iron clusters have the potential for additional formal oxidation states. Because not all of these states have been found in proteins or model compounds, it is possible that some oxidation states may be unstable. For a given Fe S protein only one redox couple is used the other possible states appear to be excluded by restrictions of the protein structure. This selection rule is illustrated with two 4Fe 4S low-molecular-weight electron transfer proteins ferredoxin and high-potential iron protein (HiPIP). The 4Fe 4S clusters in both proteins were shown by X-ray crystallography to be virtually identical. However, the redox potential and oxidation states for the two proteins are vastly... 

High-potential iron proteins, 45 313-314, 344 cluster stability, 45 324-332 function, 45 315-316 residues, 45 322-344 structure and, 45 317-322 redox properties, 45 333-344 solvent accessibility, 45 330, 332-333 source and function, 45 314-316 structure, 45 316-322 hydrogen bonding and, 45 321-322 intermolecular aggregation, 45 322 primary, 45 317-318 secondary and tertiary, 45 318-321... 

The [4 Fe-4 S] cores have been one of the most intriguing inorganic structures involved in biological systems. Carter et al. (1977) 191 demonstrated that the same basic structure is present in the two [4 Fe—4 S] centers of the 8 Fe ferredoxin of Peptococcus aerogenes (E 0 = - 400 mV)2) and in the high potential iron protein (HiPIP) isolated from the purple photosynthetic bacterium Chromatium vinosum... 

STRUCTURE-FUNCTION CORRELATIONS IN HIGH-POTENTIAL IRON PROTEINS... 

Most high-potential iron proteins have been isolated from purple photosynthetic bacteria and vary in size from 6 to 10 kDa the tertiary structures of many have been determined in the crystalline and/or solution states, including HiPIPs from C. vinosum (1,49,52,108-110), Ectothiorhodospira halophila 1 48, 102, 111, 112), Ectothiorhodospira... 

Fluorine-labeled analogues of C. vinosum high-potential iron protein have been investigated by F NMR spectroscopy. By incorporation of specific fluorine-labeled amino acid residues, one can insert unique probes at well-defined locations within the protein core. The synthesis and purification of 2-, 3-, and 4-fluorophenylalanine (abbreviated 2-F-, 3-F-, and 4-F-Phe, respectively), 3-fluorotyrosine (3-F-Tyr), and 5-fluorotr3q)tophan (5-F-Trp) derivatives of C. vinosum HiPIP, the assignment of F NMR resonances, the measurement of longitudinal relaxation times, and the temperature dependence of F and resonances have all been reported 42, 43, 136). These measurements were used to examine structural perturbations of mutants, the dynamics of interaction of residues with the cluster, and solvent accessibility, and as a test of the relative contribution of cross-relaxation to magnetization decay. 

Iron-sulfur proteins occur in animal, plant, and bacterial cells. The proteins are characterized by the presence of 1-0, 2-2, 4rA, 6-6, or 8-8 atoms of iroursulfide. Only the structure of clostridial rubredoxin, a 1-0 protein, is knoum. It contains iron ligated to four sulfur atoms of cysteine residues of the polypeptide. With the exception of the ""high potential iron protein, all the proteins show unexpectedly low redox potentials and function in biological oxidationr-reduc-tion reactions. 

The complete structure of clostridial rubredoxin has been solved by Jensen and his associates using x-ray analysis (49), and the structure of the iron-sulfur center of the high potential iron protein, but not of the polypeptide, has been determined by x-ray analysis by Kraut and associates (50). Both of these are relatively atypical proteins in this class, either having no inorganic sulfide or having a very high redox potential. So far, we still have no solution from x-ray work for the 2-iron-2-sulfur or the 8-iron-8-sulfur type protein. 

Structure.Bacterial ferredoxin shows a very similar band pattern (Fig. 22, third spectrum), indicating a similar distortion of the cube. The spectrum of HiPIP (high-potential iron protein) from C. vinosum (Fig. 22, second spectrum) appears to be simpler and was interpreted as indicating a relatively undistorted cube structure, but at higher resolution the spectrum has been found to show band splittings, which are more pro-... 

Redox Proteins.—The study of redox proteins by ilf-ray analysis has been very productive during the year. High-resolution structures of ferri- and ferro-cytochrome c, cytochrome b, cytochrome c, ferredoxin, rubredoxin, high-potential iron protein, and two flavodoxins have now been worked out, although not all were published in 1971. 

It must be stressed at the outset that compared to the state of refinement achieved in some protein structures at high resolution (e.g., rubredoxin [1], high potential iron protein [2], and the complex of bovine trypsin and bovine pancreatic trypsin inhibitor... 

Synthetic iron-sulphur cluster compounds of general structure (11) serve as analogues of the active sites of (Fe4S4) ferredoxins and high-potential iron proteins... 

Structural studies on electron transfer metalloproteins provide an important origin for discussion of the electron transfer processes themselves.The reduction potentials of a number of cytochromes c, cyt c copper blue proteins plastocyanin, Pc azurin, Az stellacyanin, St and HiPIP, or high potential iron protein, from Chromatium vinosum have been determined using spectro-... 

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