Lysozyme Macromolecule

B. R. Brooks and M. Karplus. Normal modes for specific motions of macromolecules Application to the hinge-bending mode of lysozyme. Proc. Natl. Acad. Sci. USA, 82 4995-4999, 1985. 

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.)... 

At best, van der Waals interactions are weak and individually contribute 0.4 to 4.0 kj/mol of stabilization energy. ITowever, the sum of many such interactions within a macromolecule or between macromolecules can be substantial. For example, model studies of heats of sublimation show that each methylene group in a crystalline hydrocarbon accounts for 8 k[, and each C—IT group in a benzene crystal contributes 7 k[ of van der Waals energy per mole. Calculations indicate that the attractive van der Waals energy between the enzyme lysozyme and a sugar substrate that it binds is about 60 k[/mol. 

Harada, A. and Kataoka, K. (1998) Novel polyion complex micelles entrapping enzyme molecules in the core preparation of narrowly-distributed micelles from lysozyme and poly(ethylene glycol)-poly(aspartic acid) block copolymer in aqueous medium. Macromolecules, 31, 288-294. 

With the rapid advances in macromolecule crystallography, the PDB (http //www.rcsb.org/pdb/) currently contains about 12,600 macromolecular NMR or crystal structures. While this may not represent all macromolecular structures, it does represent the large majority. Most of the major scientific journals require simultaneous deposition of macromolecular crystal data into the PDB as the journal article is published. Besides structural proteins, and the classic crystal structures such as hemoglobin and lysozyme, the data base includes many enzymes or representative enzymes from classes that could be good targets for chemotherapy. 

Brooks, B. R. and Kamlus, M. (1985) Normal Modes for Specific Motions of Macromolecules Application to the Hinge-Bending Mode of Lysozyme, Proc. Natl Acad. Sci. USA 82, 4995-4999. 

Pincus, M. R. and Scheraga, H. A. (1979) Conformational energy calculations of enzyme-substrate and enzyme-inhibitor complexes of lysozyme. 2. Calculation of the structures of complexes with a flexible enzyme., Macromolecules 12, 633-644. 

Our understanding of the principles underlying the catalytic activity of enzymes has increased greatly in recent years. Enzymes are proteins and we know now that the polypeptide chain of a globular protein molecule will assume spontaneously a well-defined conformation (3). This native conformation of the macromolecule is essential to the function of the enzyme. Recent studies show that enzyme crystals, into which substrate molecules may penetrate by diffusion, have similar catalytic characteristics as enzyme solutions (4) and this result tends to strengthen our belief that the conformation of the enzyme molecule, as deduced from X-ray diffraction studies of enzyme crystals, is identical, or at least very similar, to the conformation responsible for the catalytic activity under physiological conditions. The structures of some enzymes, e.g., lysozyme (5), ribonuclease (6), and carboxypeptidase A (7), have been determined they are all consistent with the general belief that... 

A major question in protein chemistry is why does one salt (or salt concentration) induce Ctystallization while most other conations lead to precipitation of a concentrated protein solution A quasi-elastic light scattering study of the effect of salts on lysozyme and concanavalin A precipitation concluded that salts that encourage precipitation lead to an increase in macromolecule polydispersity and size... 

Although only BSA was used as a model macromolecule In the second study, Initial results have also Indicated that zero-order release rates were obtained for over one month for lysozyme and 8-lactoglobulin when they were Incorporated Into hemispheric matrices. The hemisphere systems have not yet been tested In vivo. However, future studies will explore the Inulln model used in the first section of this paper. 

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). 

Ionic Strengths If the protein-polymer complex is formed as a result of electrostatic interactions, increased ionic strength should serve to reduce the attraction between the oppositely charged macromolecules, and decrease the precipitation efficiency. This is observed at pH 4.2 in Figures 3 and 4 for lysozyme and ovalbumin, respectively, and in Figure 5 for lysozyme at pH 5.8 and 7.5. 

Evidence for the binding of protective molecules to important cellular macromolecules continues to appear. The protection of GED against inactivation of trypsin, lysozyme, and aldolase was considered not due to radical scavenging, but to mixed disulfide formation. Protection of DM by diamino disulfides was attributed to bound disulfide and protection of lactate dehydrogenase and catalase by serotonin was also attributed to complex formation, possibly with the metal ions in the enzymes. 

By using a surface radioactivity technique, the penetration of the hydrophobic and flexible 1-14C-acetyl--casein and the rigid and globular 1-14C-acetyl-lysozyme molecules into phospholipid monolayers in different physical states was monitored. The adsorption of ff-casein to lecithin mono-layers is described by a model in which it is assumed that the protein condenses the lecithin molecules so that the degree of penetration is a function of the lateral compressibility of the phospholipid monolayer. The interaction of ff-casein with phospholipid monolayers is dominated by the hydrophobicity of the macromolecule, but lysozyme tends to accumulate mostly beneath phospholipid monolayers in this situation, electrostatic interactions between the lipid and protein are important. 

---