Lysozyme structure

Bovine a-lactalbumin is one of the two enzymes in lactose synthetase, and its amino acid sequence shows striking similarities to that of lysozyme.118 A model based on the lysozyme model has been built, and the side-chain interactions found are convincing, showing that the model is essentially correct. The active cleft in the crystal is, however, shorter than that in the model, and is consistent with a mono- or di-saccharide as the substrate. Thus, the lysozyme structure may serve as a model for some enzymes that synthesize and hydrolyze carbohydrates. 

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).

Prior to the crystallization of jack bean urease it was assumed by the biochemical community that enzymes had no ordered structure. In 1965 the first crystallographic evidence for the mechanism by which enzymes work when Phillips and his group solved the lysozyme structure [6], Details of the structure indicated how the enzyme could bind the oligosaccharides present in its target, bacterial cell wall peptidoglycans, and could respond to the binding event by changing its structure. 

Perez, C., De Jesus, P, and Griebenow, K. (2002), Preservation of lysozyme structure and function upon encapsulation and release frompoly(lactic-co-glycolic) acid microspheres prepared by the water-in-oil-in-water method, Int. J. Pharm., 248,193-206. 

As one of the extensively investigated protein families, hundreds of lysozyme structures are deposited in the Protein Data Bank, including wild type from different sources and numerous mutants. Also available are the sfructures... 

In any event it was the analysis of baboon a-lactalbumin crystals for which the first X-ray crystal structure was produced, initially at 0.6 nm (6 A) and 0.45 nm (4.5 A) (Phillips etal., 1987 Smith etal., 1987). More recently, the structure has been refined at 0.17-nm (1.7-A) resolution, enabling comparison with the high-resolution c-type lysozyme structure (Acharya et al., 1989) (see Fig. 7). 

Sternberg, M. J. E., Grace, D. E. P., and Phillips. D. C. Dynamic information from protein crystallography. An analysis of temperature factors from refinement of the hen egg-white lysozyme structure. J. Molec. Biol. 130, 231-253 (1979). 

Furthermore, it has been proposed that DMSO and alcohols can be utilized to stabilize reversibly unfolded states (Arakawa and Goddette, 1985 Bhattachar-jya and Balaram, 1997). For example, DMSO has been observed to stabilize a partially unfolded conformation of lysozyme (pH 3.0) (Bhattacharjyaand Balaram, 1997). Lysozyme in 10% DMSO showed little change in structure by nuclear magnetic resonance (NMR) when compared with aqueous conditions. The lysozyme structure in 50% DMSO resembled an early kinetic intermediate observed in the refolding process. Conversely, a highly unfolded structure in 100% DMSO has been reported, probably due to the polar aprotic nature of the solvent (Jackson and Mantsch, 1991). 

This chapter is structured as follows In Sect. 6.2, a basic introduction to molecular refinement is presented, stressing particularly relevant aspects. Section 6.3 reviews the recent work by Falklof et al., describing how the 2 x 2 x 2 supercell for the lysozyme structure was obtained. Section 6.4 reviews some modern advances in DFT, focusing on dispersion-corrected DFT, while Sect. 6.5 describes the effects of DFT optimization of atomic coordinates on the agreement between observed and calculated X-ray structure factors. The aim is to determine an optimal electronic-structure computational procedure for quantum protein refinement, and we consider only the effects of minor local perturbations to the existing protein model rather than those that would be produced by allowing full protein refinement. 

We showed that an ensemble of eight lysozyme structures, comprising 19335 atoms, could reproduce the observed conformational flexibility of lysozyme in a way that was consistent with both the observed X-ray scattering data and standard requirements for a chemically reasonable stmcture. By using an ensemble we hoped to better reflect the anisotropy of the system without the need to introduce anisotropic atomic temperature factors (B factors). In this way the total number of parameters... 

A glycosidase, lysozyme, was the first enzyme whose X-ray strueture was solved, and the meehanism of aetion proposed at the time (1966) postulated general aeid eatalysis by Glu35 the proton was transferred from Glu35 as the CA) bond of the substrate was broken. An example of intramoleeular general aeid eatalysis (the aeeelerated hydrolysis of salicyl p-D-glueopyranoside) was already known, but the lysozyme structure prompted a search for further model systems. 

Every second protein domain in PDB is represented by more than one PDB entry 20% of proteins have two structures, and the remaining 30% more than two structures. Some of them are mutants (e.g., 400 of T4 lysozyme structures from Brian Matthews s laboratory) but in most cases, these multiple structures represent snapshots of the pocket conformational diversity. Furthermore, many entries contain more than one chain in an asymmetric unit. These protein structures related by noncrystallographic symmetry can also be used as a source of multiple pocket conformations. The noncrystallographic symmetry-related subunits increase the number of domains already represented by multiple experimental conformations from 50% to the overall level of 75% (Fig. 2). About 5% of the domains are represented by more than 30 copies. 

Pathology in Cambridge. Here, he made several useful contributions in research on inflammation, gastric function and secretion of mucus this latter area of research led him on to a major study of lysozyme structure and function that lasted until 1938. From Cambridge, Florey moved to the University of Sheffield as Professor of Pathology in 1932, but this proved to be a brief stay since he was offered the Chair of Pathology at the Sir William Dunn School of Pathology in Oxford three years later. This was to become the focus of penicillin research some four years later. 

The nnfolding of lysozyme structure was reported to be induced by PEF (35 kV cm and 300 ps) this was accompanied by the cleavage of disulfide bonds and self association aggregation when the applied PEF dosage was higher than the critical level (Zhao et al., 2007). 

A summary of general features is described below as an introduction to later topics. Excellent and extensive reviews on lysozyme structure-function relation-... 

Certain properties of lysozyme, which are common to / -glucan endo-hydrolases, have been explained following the elucidation of the structure of the active site. It is therefore relevant to discuss the current concepts of lysozyme structure and action and to compare these with the rather fragmentary observations so far made on the action of the various / -glucan endo-hydrolases. 

Poole, P.L., The role of hydration in lysozyme structure and activity Relevance in protein engineering and design, J. Food Eng., 22, 349, 1994. 

Buijs, J., Speidel, M., Oscarsson, S. (2000) The stability of lysozyme adsorbed on silica and gallium arsenide surfaces Preferential destabilization of part of the lysozyme structure by gallium arsenide. J Colloid Interface Sci, 226 (2), 237-245. 

Grutter, M.G., L.H. Weaver, and B.W. Mattews. 1983. Goose lysozyme structure An evolutionary link between hen and bacteriophage lysozyme. Nature 303 828-831. 

Which lysozyme structure did you start from Which lysozyme structure did you compare in bound systems It is necessary to use the highest resolution structures since the side chains move during refinement. 

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