Protein structural correlation

Band L, Bencini A, Benelli C, Gatteschi D, Zanchini C (1982) Spectral-Structural Correlations in High-Spin Cobalt(II) Complexes. 52 37-86 Band L, Bertini I, Luchinat C (1990) The H NMR Parameters of Magnetically Coupled Dimers-The Fe2S2 Proteins as an Example. 72 113-136 Baran EJ, see MuUer A (1976) 26 81-139... 

Band shape-based analyses similar to those used for ECD have also been applied to FTIR and Raman spectra with reasonable success (Williams and Dunker, 1981 Dousseau and Pezolet, 1990 Lee etal., 1990 Sarver and Kruger, 1991 Pribic etal., 1993 Baumruk etal., 1996). Clearly, spectra-structure correlations based only on folded proteins would lead... 

Myelin in situ has a water content of about 40%. The dry mass of both CNS and PNS myelin is characterized by a high proportion of lipid (70-85%) and, consequently, a low proportion of protein (15-30%). By comparison, most biological membranes have a higher ratio of proteins to lipids. The currently accepted view of membrane structure is that of a lipid bilayer with integral membrane proteins embedded in the bilayer and other extrinsic proteins attached to one surface or the other by weaker linkages. Proteins and lipids are asymmetrically distributed in this bilayer, with only partial asymmetry of the lipids. The proposed molecular architecture of the layered membranes of compact myelin fits such a concept (Fig. 4-11). Models of compact myelin are based on data from electron microscopy, immunostaining, X-ray diffraction, surface probes studies, structural abnormalities in mutant mice, correlations between structure and composition in various species, and predictions of protein structure from sequencing information [4]. 

Pazos, F., Olmea, O., and Valencia, A. (1997) A graphical interface for correlated mutations and other protein structure prediction methods. Comput. Appl. Biosci. 13, 319-321. 

The major reasons for using intrinsic fluorescence and phosphorescence to study conformation are that these spectroscopies are extremely sensitive, they provide many specific parameters to correlate with physical structure, and they cover a wide time range, from picoseconds to seconds, which allows the study of a variety of different processes. The time scale of tyrosine fluorescence extends from picoseconds to a few nanoseconds, which is a good time window to obtain information about rotational diffusion, intermolecular association reactions, and conformational relaxation in the presence and absence of cofactors and substrates. Moreover, the time dependence of the fluorescence intensity and anisotropy decay can be used to test predictions from molecular dynamics.(167) In using tyrosine to study the dynamics of protein structure, it is particularly important that we begin to understand the basis for the anisotropy decay of tyrosine in terms of the potential motions of the phenol ring.(221) For example, the frequency of flips about the C -C bond of tyrosine appears to cover a time range from milliseconds to nanoseconds.(222)... 

Since the rate constants of bimolecular diffusion-limited reactions in isotropic solution are proportional to T/ these data testify to the fact that the kt values are linearly dependent on the diffusion coefficient D in water, irrespective of whether the fluorophores are present on the surface of the macromolecule (human serum albumin, cobra neurotoxins, proteins A and B of the neurotoxic complex of venom) or are localized within the protein matrix (ribonuclease C2, azurin, L-asparaginase).1 36 1 The linear dependence of the functions l/Q and l/xF on x/t] indicates that the mobility of protein structures is correlated with the motions of solvent molecules, and this correlation results in similar mechanisms of quenching for both surface and interior sites of the macromolecule. 

As shown above, the intrinsic fluorescence spectra of proteins as well as coenzyme groups and probes shift within very wide ranges depending on their environment. Since the main contribution to spectral shifts is from relaxational properties of the environment, the analysis of relaxation is the necessary first step in establishing correlations of protein structure with fluorescence spectra. Furthermore, the study of relaxation dynamics is a very important approach to the analysis of the fluctuation rates of the electrostatic field in proteins, which is of importance for the understanding of biocatalytic processes and charge transport. Here we will discuss briefly the most illustrative results obtained by the methods of molecular relaxation spectroscopy. 

There is a correlation between the backbone conformations which commonly flank disulfides and the frequency with which disulfides occur in the different types of overall protein structure (see Section III,A for explanation of structure types), although it is unclear which preference is the cause and which the effect. There are very few disulfides in the antiparallel helical bundle proteins and none in proteins based on pure parallel /3 sheet (except for active-site disulfides such as in glutathione reductase). Antiparallel /3 sheet, mixed /8 sheet, and the miscellaneous a proteins have a half-cystine content of 0-5%. Small proteins with low secondary-structure content often have up to 15-20% half-cystine. Figure 52 shows the structure of insulin, one of the small proteins in which disulfides appear to play a major role in the organization and stability of the overall structure. 

Successful examples of the sort of correlations postulated above would add additional independent pieces of information for use in a combined strategy of noncrystallographic protein structure determination. Empirical regularities such as the handedness of crossover... 

In a very broad overview of the structural categories one can state several statistical correlations with type of function. Hemes are almost always bound by helices, but never in parallel a//3 structures. Relatively complex enzymatic functions, especially those involving allosteric control, are occasionally antiparallel /3 but most often parallel a//3. Binding and receptor proteins are most often antiparallel /3, while the proteins that bind in those receptor sites (i.e., hormones, toxins, and enzyme inhibitors) are most apt to be small disulfide-rich structures. However, there are exceptions to all of the above generalizations (such as cytochrome cs as a nonhelical heme protein or citrate synthase as a helical enzyme), and when one focuses on the really significant level of detail within the active site then the correlation with overall tertiary structure disappears altogether. For almost all of the dozen identifiable groups of functionally similar proteins that are represented by at least two known protein structures, there are at least... 

Diamond (1966) has applied a filtering procedure in the refinement of protein structures, in which poorly determined linear combinations are not varied. In charge density analysis, the principal component analysis has been tested in a refinement of theoretical structure factors on diborane, B2H6, with a formalism including both one-center and two-center overlap terms (Jones et al. 1972). Not unexpectedly, it was found that the sum of the populations of the 2s and spherically averaged 2p shells on the boron atoms constitutes a well-determined eigenparameter, while the difference is very poorly determined. Correlation between one- and two-center terms was also evident in the analysis. 

Miscellaneous bRC. - The bRC of R. sphaeroides contains one accessible cysteine at the H subunit (His H-156). Poluektov et al.m have bound a specific nitroxide spin label to this Cys and used temperature-dependent multifrequency (9 and 130 GHz) EPR to determine the motion of the protein. It was found that the restricted dynamics can be described as fast libration in a cone with a correlation time of >10 9 s. Several dynamically nonequivalent sites were observed that indicate conformational substates of local protein structure. 

Bonds and Forces - These properties are the mediators affecting the changes in size and conformation. Van der Waal forces, ionic bonds, hydrogen bonds, covalent bonds, and hydrophobic bonds all play a part in the original protein structure as well as in the modifications leading to altered functionality. Adequate correlations of these with functional properties are the subjects of "Functional Evaluations" 3). 

That is, we must learn how amino acid content and molecular configuration of food proteins are related to their functional properties. This goal is made more difficult by the fact that secondary, tertiary, and quarternary structures of proteins are likely to be quite different when exerting functional effects in food systems as compared to structures of the same proteins in dilute solutions and in their native states. The way in which specific actions of proteases affect protein structure must also be studied so that correlations with changes in functional properties can be made (61). 

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