Lysozyme molecular models

The visuahzation of hundreds or thousands of connected atoms, which are found in biological macromolecules, is no longer reasonable with the molecular models described above because too much detail would be shown. First of aU the models become vague if there are more than a few himdied atoms. This problem can be solved with some simplified models, which serve primarily to represent the secondary structure of the protein or nucleic acid backbone [201]. (Compare the balls and sticks model (Figure 2-124a) and the backbone representation (Figure 2-124b) of lysozyme.)... 

A half-chair conformation of a crystalline monosaccharide has not been observed. A half-chair conformation for the fourth 2-acetamido-2-deoxy-/3-D-glucopyranosyl residue (residue D) in the lysozyme substrate has not been detected, although, on the basis of model fitting, its presence has been suggested (see p. 96). 2-Acetamido-2-deoxy-/3-D-glucosyl groups were added to a molecular model constructed by use of data obtained from the nature of the enzyme-trisaccharide complex it was implicit that the lifetime of the half-chair conformation would be quite short. 

The combination of molecular modeling with genetic engineering to enhance protein stability has been successful in certain cases. For instance, introducing carefully sited novel disulfide bonds increased protein stability in T4 lysozyme (11-13) and in X-repressor (14). However, the results in other proteins, for instance, in subtilisin (15,16) and in dihydrofolate reductase (17) have been less predictable. 

Although not very numerous, sweet macromolecules, both natural (Morris, 1976) and synthetic (Zaffaroni, 1975), are crucial for an understanding of the mechanism of the sweet receptor. The best known among proteins with a very strong sweet taste are brazzein (Ming and HeUekant, 1994), monellin, and thaumatin (Kurihara, 1992). Figure 5 shows molecular models of these three proteins. Other two known sweet proteins are mabinlin (Kurihara, 1992) and hen egg white (HEW) lysozyme (Maehashi and Udaka, 1998), whereas miraculin and curculin, which taste sweet when combined with sour substances, can be better described as taste-modifier proteins (Kurihara, 1992). 

Figure 3.12 The enzyme lysozyme viewed to illustrate the active site cleft, (a) Skeletal diagrams in stereo (kindly prepared by Dr J. Rafteiy). (b) Beevers molecular model (with permission to be reproduced here), (c) Schematic of the alternating NAG-NAM substrate and the bond cleaved, catalysed by the enzymatic residues asp 52 and glu 35. Based on the coordinates of Diamond (1974).

A FIGURE 14.28 Molecular model of lysozyme without and with a bound substrate molecule (yellow). 

Figure 14.25 (a) A molecular model of the enzyme lysozyme. Note the characteristic cleft, which is the location of the active site, (b) Lysozyme with a bound substrate molecule. 

Hayward, S., Kitao, A., Berendsen, H.J.C. Model-free methods to analyze domain motions in proteins from simulation A comparison of normal mode analysis and molecular dynamics simulation of lysozyme. Proteins 27 (1997) 425-437. 

Figure 2-124. The most common molecular graphic representations of biological molecules (lysozyme) a) balls and sticks b) backbone c) cartoon (including the cylinder, ribbon, and tube model) and of inorganic molecules (YBajCujO , d) polyhedral (left) and the same molecule with balls and sticks (right),...

The model systems, discussed here, contain one type of well-defined protein and one type of well-characterized solid surface in an aqueous medium containing one type of low molecular-weight electrolyte. Table 2 summarizes some relevant properties of the proteins. Lysozyme (LSZ)... 

The most popular model describing small-angle rotational movements of aromatic rings is the model of torsional vibrations around the C —Cp and Cfi—Cy bonds/30,70) This model has been used in simulations of motions by the methods of molecular dynamics/75 76) However, the results are not always satisfactory. In some cases, for example, for lysozyme,(77) the experimental data do not agree well with the results of simulations the observed motions are slower and less extended than predicted. 

Figure 14.12. Superimposition of molecular structures with HyperChem. Pigeon lysozyme structure (red) derived from homology modeling with Swiss-PDB Viewer is overlapped against chicken lysozyme structure, pdb1 lyz.ent (black). Two catalytic residues, Glu35 and Asp 52 (chicken lysozyme), are highlighted (green).

Thus, Wilson and colleagues (see White et al., 1977 Wilson et al., 1977) were led to propose Model II (referred to as Model I by Prager and Wilson, 1988), the essential feature of which is that the a-lactalbu-min-lysozyme duplication occurred long before the mammary gland evolved and before the above repdlian split. They believed that this model was in accord with the known sequence resemblances, did not need to invoke rate acceleration, and was, therefore, consistent with the molecular evolutionary clock. 

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