Lysozyme cleft region

Ile-27, runs to Asp-88, and is partially occupied by water molecules. The channel is blocked by Tyr-103 (which is in the cleft region). There are corresponding cavities in hen egg-white lysozyme. The second cavity in the vicinity of Ser-91 is occupied by internal water molecules in egg-white lysozyme. This residue becomes Asp (residue 88) in a-lactalbumin. Due to calcium binding properties in a-lactalbumin, the locations of internal water molecules are somewhat different from those in lysozymes that do not bind calcium. 

In conclusion, attention is drawn to several puzzling features the differences found in the cleft region suffice to predict that a-lactalbumin would have no cell lytic activity. It remains an anomaly, however, that weak activity has been demonstrated for a-lactalbumin from various sources by McKenzie and White (1987) (Section X), and it is an unresolved problem as to how such activity could be explained, except by the possible involvement of His-32 in a-lactalbumin as an active site residue, in place of Glu-35, which appears in lysozyme (for further discussion see Section X). In addition, there are numerous discrepancies between the reactivities of a-lactalbumin and lysozyme. The former is generally a more reactive protein (Section IX), and these differences could not have been predicted by consideration of the above models, nor from the X-ray structural analysis. 

Figure 51. Solvent mean-square displacement for water in the cleft region of lysozyme. The mean-square displacement is plotted versus time (ps) for water within a 6.0- A sphere around the apolar atoms (a) Asp-48 C3 (b) Ser-72 0s (c) Asn-46 C3 (d) Gly-71 C . The dashed line indicates the linearly extrapolated diffusional motion.

An algorithm based upon a dynamic programing concept has been described by Jernigan et al. for minimizing the free energy of a polypeptide, and utilized for secondary structure prediction. In a study with the aid of UNICEPP of the binding of flexible substrate molecules within the cleft region of lysozyme (EC... 

Tryptophan 108 is recognized to be an active site in promoting the hydrolysis of 3(l,4)-glycosidic linkages between amino sugar residues in polysaccharide components of the bacterial cell walls. This residue is shown to occupy the cleft as well as trjrptophan 62 and 63, and is in a hydrophobic region. Tryptophan residues 62 and 108 are indispensable for the action of lysozyme, and tryptophan 62 is known to be the only binding site for the complex formation (13). Oxidation of tryptophan-108 is expected... 

There is a third region of a protein that is neither on the surface nor in the interior but that is in a cleft. Such regions are often associated with enzyme action and examples show they have (1) intermediate mobility (e.g., tryptophan 62 of lysozyme or the tyrosine of carboxypeptidase) and (2) unfavorable energetics of exposed groups—the entatic state. 

In a molecular dynamics study of native and substrate-bound hen egg-white lysozyme, Post et al. (1986) found the structural features analyzed agreed well with the results of X-ray studies at 0.15-nm (1.5 A) resolution, except for some surface residues. Appreciable differences were found in residue mobilities between the simulations of the native and substrate-bound states in the region of the enzyme that is in direct contact with the substrate and in a region that is distant from the active site cleft. 

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