Protein conformational features

Studies on the Conformational Features of Neomycin-B and its Molecular Recognition by RNA and Bacterial Defense Proteins... 

Of great interest to the molecular biologist is the relationship of protein form to function. Recent years have shown that although structural information is necessary, some appreciation of the molecular flexibility and dynamics is essential. Classically this information has been derived from the crystallographic atomic thermal parameters and more recently from molecular dynamics simulations (see for example McCammon 1984) which yield independent atomic trajectories. A diaracteristic feature of protein crystals, however, is that their diffraction patterns extend to quite limited resolution even employing SR. This lack of resolution is especially apparent in medium to large proteins where diffraction data may extend to only 2 A or worse, thus limiting any analysis of the protein conformational flexibility from refined atomic thermal parameters. It is precisely these crystals where flexibility is likely to be important in the protein function. 

Although abundant evidence supports the existence of snch an antoimmnne phenomenon, the causative event that heralds this self-directed immune-mediated attack remains uncertain. A number of mechanisms have been proposed to afford a molecular-level explanation of autoimmunity. One such explanation is molecular mimicry. Molecular mimicry occurs when a protein associated with a foreign substance bears structural similarities to a protein found in the host. For example, if a person experiences an infection from bacteria, there is a possibility that a protein in the bacterium shares certain similar geometrical and conformational features with a protein already existing in the person. Thus, an immune response directed against the bacteria will cross-react with organs in the host organism. 

In the spectrum of deoxymyoglobin most of the spectral features between DSS and —10 ppm, and three resonances of intensities three protons at +0.6, +0.3 and 0 ppm (Fig. 30) were found to be independent of temperature, and hence seem to be determined essentially by the protein conformation in the molecule (Shulman et al. (100, 101)). 

Figure 2.20 Enzyme structure can be divided into primary (amino acid sequence), secondary (chain folding), tertiary (full 3D conformation) and quaternary (association of more than one protein chain) features.

Analysis of the CD spectrum has yielded values of 14% a helix and 31 % p strand, with a possible increase in helix content observed with increase of temperature (Loucheaux-Lefebvre et al., 1978). In a more recent study (Ono et al., 1987), a lower fraction of a helix was calculated, but the results vary with the method of calculation. Structure prediction methods have also been applied to this protein and have given results that encourage the view that K-casein has a number of stable conformational features. Loucheaux-Lefebvre et al. (1978) applied the Chou and Fasman (1974) method and predicted an a-helical content of 23%, with 31% P strand and 10% p turns. Raap et al. (1983) preferred the method of Lim (1974) to predict a-helix and P-strand content, because the method of Chou and Fasman, as published in 1974, was considered to overpredict these elements (Lenstra, 1977). They also tested their predictions for the structure about the chymosin-sensitive bond using the later boundary analysis method... 

Fodje MN, Al-Karadaghi S. Occurrence, conformational features and amino acid propensities for the pi-helix. Protein Eng 2002 15 353-358. 

Table V shows that the vast majority of the titratable groups of the smaller protein molecules have pK nt values which are quite close to the values predicted from the pK s of model compounds. This feature of protein titration curves has been well known for a long time, and is accepted as normal. It is however really an astonishing result, for it implies that most of the titratable groups of the smaller protein molecules are in as intimate contact with the solvent as similar groups on smaller molecules, and that they are able to accept or release hydrogen ions in this location without requiring any modification of the protein conformation in the vicinity of the titratable group. Since most of the proteins examined have been globular proteins, tightly folded so as to exclude solvent from most of the interior portions, the titratable groups must be nearly always at the surface.

During hydride ion transfer, careful analysis of the secondary structural features of the protein in the ternary complex reveals that the overall conformational features of the protein remain undisturbed. The conformational angles of the residues in the MET loop were analyzed in detail due to its proximity to the substrate. The MET loop is composed of amino acid residues Ala9 through Leu24. Comparison of the initial, transition, and final states of the MET loop during hydride ion transfer reveals that (a) between the initial state and the transition state, the angle... 

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