Biopolymers three-dimensional structure

SCR (structurally conserved regions) sections of a biopolymer sequence that are identical to that of another sequence, for which there is a known three-dimensional structure... 

NMR methods have also been used extensively to determine the configuration and conformation of both moderate-size molecules and synthetic polymers, whose primary molecular structure is already known. During the past decade high resolution NMR, particularly employing 2D and 3D methods, has become one of only two methods (x-ray crystallography is the other) that can be used to determine precise three-dimensional structures of biopolymers—proteins, nucleic acids, and their cocomplexes—and NMR alone provides the structure in solution, rather than in the solid state. 

Our concern in this section, however, is not the application to biopolymers of methods that are equally applicable to smaller molecules. Rather, we discuss here a totally different approach to the determination of precise three-dimensional structures of these molecules, in which NMR data play a key role. We illustrate the concept with proteins, which have yielded particularly useful information, but the general approach can also be used with nucleic acids and with complexes of a protein and a nucleic acid. 

The Encyclopedia of NMR1 contains a very large number of articles on biological applications of NMR, including discussions of the methodology used for three-dimensional structure determination, along with presentations on individual biopolymers. 

Proteins are one of the main classes of biopolymers found in living organisms. They can adopt a large variety of structural patterns, which makes them essential cell constituents mostly involved in recognition processes. Their molecular recognition ability is remarkable in catalysis because enzymes have evolved to accommodate transition states in their active site to lower the kinetic barriers of most biochemical reactions. This ability is connected to appropriate primary sequences, and it allows the proteins to fold into well-defined three-dimensional structures. However, the accuracy of the primary sequence, which is ensured by the translation of genomic sequences in... 

Living cells produce a remarkable variety of macromolecules that serve as structural components, biocatalysts, hormones, receptors, or storehouse of genetic information. These macromolecules, proteins, nucleic acids, and polysaccharides are biopolymers constructed of monomer units or building blocks for proteins the monomer units are a-amino acids. Proteins may contain substances other than a-amino acids, for example, glycoproteins also contain carbohydrates. The three-dimensional structure and the biological properties of proteins, however, are largely determined by the kinds of amino acids present, the order in which they are linked together in the polypeptide chain, and thus the spatial relationship of one a-amino acid to another. 

The most obvious data in a typical three-dimensional structure record, regardless of the hie format in use, is the coordinate data, the locations in space of the atoms of a molecule. These data are represented by (x, y, z) triples, distances along each axis to some arbitrary origin in space. The coordinate data for each atom is attached to a list of labeling information in the structure record which element, residue, and molecule each point in space belongs to. For the standard biopolymers (DNA, RNA, and proteins), this labeling information can be derived starting with the raw sequence. 

Implicit in each sequence is considerable chemical data. We can infer the complete chemical connectivity of the biopolymer molecule directly from a sequence, including all its atoms and bonds, and we could make a sketch, just like the one described earlier, from sequence information alone. We refer to this sketch of the molecule as the chemical graph component of a three-dimensional structure. Every time a sequence is presented in this book or elsewhere, remember that it can encode a fairly complete description of the chemistry of that molecule. 

Figure 5.4. Structure query from NCBI with the structure IBNR (Bycroft et al., 1991). The Structure Summary links the user to RCSB through the PDB ID link, as well as to validated sequence files for each biopolymer, sequence, and three-dimensional structure neighbors through the VAST system. This system is more efficient than the RCSB system (Fig. 5.2) for retrieval because visualization, sequence, and structure neighbor links are made directly on the structure summary page and do not require fetching more Web pages.

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