Crystal structure of macromolecules

In this section we describe the classical presentation of the crystal structure of macromolecules. These include two synthetic polymers and two biological polymers. They provide us with insight toward the understanding of the three-dimensional structure of a compound. 

Not all polymer chains can be crystallized only those with stereoregularity can. For example, polyethylene can be crystallized because there is a regular configuration inherent in the monomer. Polypropylene, on the other hand, can be crystallized only under certain conditions. The crystal structures of these two polymers are also quite different. The former is packed in a zigzag form, whereas the latter has helical content (not, of course, 100%). We select these two polymers to illustrate the crystal structure, if any, of synthetic polymers. 

Polyethylene The C atoms form a plane of zigzag chain  

FIGURE 20.16 Projection of the unit cell on the 001 plane of polypropylene. 

FIGURE 20.18 Helices of polypropylene (a) syndiotactic (b) isotactic. [Source Adapted from Natta et al. (1960) and Wunderlich (1973). With permission from Dr. Wunderlich and Academic Press.l 

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The mechanism of carcinogenesis by PAHs is believed to involve alkylation of an informational macromolecule in a critical, but at present unknown, manner. Such an interaction with a protein has been modelled by alkylation of a peptide this showed a conformational change occurred on alkylation. It has not yet been possible to study the structure of DNA alkylated by an activated carcinogen this is because DNA is a fiber and the structural order in it is not sufficient for a crystal structure determination. However the crystal structures of some alkylated portions of nucleic acids are described, particularly some nucleosides alkylated by chloromethyl derivatives of DMBA. In crystals of these alkylation products the PAH portion of the adduct shows a tendency to lie between the bases of other nucleoside... 

De Rosa, C. Guerra, G. Petraccone, V. Pirozzi, B., Crystal structure of emptied clathrate form (8e form) of syndiotactic polystyrene, Macromolecules 1997, 30, 4147 4152... 

Although varying considerably in molecular size, any GPCR polypeptide sequence contains seven hydrophobic a-helices that span the lipid bilayer and dictate the typical macromolecule architecture. Seven transmembrane domains bundled up to form a polar internal tunnel and expose the N-terminus and three interconnecting loops, to the exterior, and the C-terminus with a matching number of loops, to the interior of the cell [1-3]. This structural information was recently confirmed by the resolution of the crystal structure of rhodopsin [4,5]. 

We shall discuss this topic under two main headings assignment of absolute configuration by imaging of (i) the secondary structure of macromolecules and (ii) the structure of a chiral molecule in a chiral crystal. 

Sequence analysis is a core area of bioinformatics research. There are four basic levels of biological structure (Table 1), termed primary, secondary, tertiary, and quaternary structure. Primary structure refers to the representation of a linear, hetero-polymeric macromolecule as a string of monomeric units. For example, the primary structure of DNA is represented as a string of nucleotides (G, C, A, T). Secondary structure refers to the local three-dimensional shape in subsections of macromolecules. For example, the alpha- and beta-sheets in protein structures are examples of secondary structure. Tertiary structure refers to the overall three-dimensional shape of a macromolecule, as in the crystal structure of an entire protein. Finally, quaternary structure represents macromolecule interactions, such as the way different peptide chains dimerize into a single functional protein. 

FIG. 19.1 Morphological models of some polymeric crystalline structures. (A) Model of a single crystal structure with macromolecules within the crystal (Keller, 1957). (B) Model of part of a spherulite (Van Antwerpen, 1971) A, Amorphous regions C, Crystalline regions lamellae of folded chains. (C). Model of high pressure crystallised polyethylene (Ward, 1985). (E) Model of a shish kebab structure (Pennings et al., 1970). (E) Model of paracrystalline structure of extended chains (aramid fibre). (El) lengthwise section (Northolt, 1984). (E2) cross section (Dobb, 1985). 

The hydrophobic effect stabilizes the three-dimensional structures of macromolecules. In the nucleic acid double helical structures, the hydrophobic bases are stacked along the helix axis and shielded from solvent by the hydrophilic sugar-phosphate backbone, which is heavily hydrated. A comparable scheme is found in many crystal structures of nucleosides and nucleotides, where the bases are stacked... 

We can envisage that this description of water movement along functional groups is not limited to the crystal structure of vitamin B12 but that it occurs generally in the hydration of biological macromolecules. If so, the concept of... 

Stipanovic AJ, Sarko A (1976) Packing analysis of carbohydrates and polysaccharides, 6. Molecular and crystal structure of regenerated cellulose II. Macromolecules 9 851-857... 

X-Ray crystallography is the method of choice for revealing atomic structures of large macromolecules and viruses. As shown in various examples in this volume, electron cryomicroscopy has emerged rapidly and has become a parallel technique to reveal additional information about virus structures, even in the situation in which the crystal structure of the virus may have already been obtained. The information that can be extracted from a hybrid approach of X-ray crystallography and electron cryomicroscopy is... 

Polyamides are an important example of polymers which do not contain pseu-doasymmetric atoms in their main chains. The chain conformation and crystal structure of such polymers is influenced by the hydrogen bonds between the carbonyls and NH groups of neighboring chains. Polyamides crystallize in the form of sheets, with the macromolecules themselves packed in planar zigzag conformations. 

The Patterson function is a map that indicates all the possible relationships (vectors) between atoms in a crystal structure. It was introduced by A. Lindo Patterson " in 1934, inspired by earlier work on radial distribution functions in liquids and powders. In crystals the directionality as well as the lengths of vectors between atoms (atomic distances) can be deduced. By contrast, in liquids and powders the geometric information that can be obtained is limited to interatomic distances, because in these the molecules are randomly oriented. While the use of the Patterson function revolutionized the determination of crystal structures of small molecules in the 1930s to 1950s, direct methods are now the most widely used methods for obtaining structures of small organic molecules. The Patterson function, however, continues to play an essential part in the determination of crystal structures of inorganic compounds and macromolecules. It is also very useful when the structure of a small molecule proves difficult to solve by direct methods. 

Such maps are primarily used to refine a trial structure, to find a part of the structure that may not yet have been identified or located, to identify errors in a postulated structure, or to refine the positional and displacement parameters of a model structure. A difference map is very useful for analyses of the crystal structures of small molecules. It is also very useful in studies of the structures of crystalline macromolecules, since it can be used to find the location of substrate or inhibitor molecules that have been soaked into a crystal once the macromolecular structure is known. A formula like that in Equation 9.1.5 is then used. When a structure determination is complete, it is usual to compute a difference electron-density map to check that the map is flat, and approximately zero at all points. 

Brinkmann M (2007) Directional epitaxial crystallization and tentative crystal structure of poly (9,9/-di- -octyl-2,7-fluorene). Macromolecules 40 7532-7541... 

Limited direct comparisons of crystal and solution structures of macromolecules can be made, based on the fact that the high-resolution NMR spectrum can be regarded as a fingerprint of the total structure [95]. Since recently it has become... 

The X-ray crystallographic sturcture of the specific macromolecular receptor is the best starting point for designing a ligand for it. Over 300 X-ray crystal structures of proteins and nucleic acids have now been solved, including several ligand-macromolecule complexes (55) most of these are available in the Brookhaven Protein Data Bank (14). NMR is also now providing the equivalent of medium ( 3 A) resolution structures for proteins up to about 100 residues (15-17, 56). 

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