Primary structure information

Amino acids link together linearly to form proteins, nucleotides link linearly to form RNA and DNA, and sugars link in a more complicated way to form complex carbohydrates. The specific sequence in which these units link together to form the final polymeric macromolecule is called its primary structure. In a way that is still very ill-understood, the primary structure ultimately controls the macromolecule s three-dimensional structure and thereby largely determines its function. There is therefore great interest in analyzing primary structural information in order to detect similarities and relationships between macromolecules. However, as we shall see later, although similar primary structures imply similar three-dimensional structures, it is possible for three-dimensional structures to resemble each other without any sequence similarity. 

The advances in protein, and especially DNA, sequencing technology means that there is now a vast amount of primary structural information relating to biological macromolecules and it is hence essential for laboratories in the field to make use of computers to analyse data on protein and nucleic acid sequences. At present (June 1994) there are more than 80000 sequences in the OWL protein sequence database [8] and there are more than 170000 nucleic acid sequences in the EMBL (European Molecular Biology Laboratory) database [9]. 

National Biomedical Research Foundation specializes in providing a database for protein primary structure. This database contains all the information from the Atlas of Protein Sequence and Structure edited by M.O. Dayhoff. In this database proteins are categorized according to their super family grouping. In addition to the primary structure information, detailed descriptions of proteins, including active site, prosthetic group, etc., are included. 

PS II [134], Primary structure information is available for linker polypeptides of Synechococcus 6301 [77] and M. laminosus [105]. The complete amino acid sequences of the and the have been established and large N-terminal... 

On the basis ofthe primary-structure information discussed above, and the known, 1 1 stoichiometry of the a- and p-polypeptides, Zuber developed a model for the light-harvesting BChl-protein complexes, as shown in Fig. 4 (A). In this model the two polypeptides span the chromatophore membrane with their hydrophobic segments consisting of 20 amino acids located in the hydrocarbon-tail region of the lipid-bilayer membrane. The polar N- and C-termini are located on the cytoplasmic and periplasmic sides, respectively. The hydrophobic amino acids in this model are present as an a-helix, in accord with the finding of a high helical content by circular dichroism. ... 

In a scenario that occurs often in a protein biochemistry lab setting, a researcher has isolated a protein of unknown function, or he/she has overexpressed a protein in Escherichia coli and wishes to characterize it. A common practice today is to submit a small amount of the protein to a core mass spectrometry laboratory for a molecular weight measurement. Using either ESI or MALDl, a molecular weight with a precision and accuracy of 0.05% or better can be measured. This, of course, depends heavily on the purity of the protein sample, the relative size of the protein, the presence or absence of post-translational modifications (PTM) (e.g., phosphorylation, glycosylation, etc.), the resolution of the mass analyzer, and so on. Primary structure information (i.e., amino acid... 

Sialyltransferases can be divided into three broad classes according to the manner of sialic acid attachment to the acceptor substrate. Under the nomenclature proposed by [92], these broad classes are designated STS, ST6, and STS to denote enzymes that transfers sialic acids to the 3 , 6" , or 8 hydroxyl positions of the underlying sugar, respectively. A summary of known and hypothetical sialyltransferases is summarized in Table 1. Thirteen distinct sialyltransferase species are named. Two additional activities, the GM3 synthase and the o2,6 to GlcNAc sialyltransferase are also listed although their primary structural information remain elusive. 

The choice of Internal coordinates as an object for optimisation Is obvious use of rotational constants maybe less so. They certainly do not give very detailed Information about the conformation of a molecule, but they are the primary structural Information derived from rotational and ro-vlb spectroscopy on small molecules. The Inclusion of dipole moments Is a must when Coulomb terms are present In the potential energy function. Charges are Included, although they are not experimentally observable quantities, because It may be desirable to lock a parameter set to data derived from photoelectron spectroscopy or from ab Initio calculations with a large basis set. Quite naturally we want to optimise on vibrational spectra, and we shall see below that It Is a bit more cumbersome In the consistent force field context than In traditional normal coordinate analysis. 

The PDB contains 20 254 experimentally determined 3D structures (November, 2002) of macromolecules (nucleic adds, proteins, and viruses). In addition, it contains data on complexes of proteins with small-molecule ligands. Besides information on the structure, e.g., sequence details (primary and secondary structure information, etc.), atomic coordinates, crystallization conditions, structure factors. 

Different techniques give different and complementary information about protein structure. The primary structure is obtained by biochemical methods, either by direct determination of the amino acid sequence from the protein or indirectly, but more rapidly, from the nucleotide sequence of the... 

The folding of a single polypeptide chain in three-dimensional space is referred to as its tertiary structure. As discussed in Section 6.2, all of the information needed to fold the protein into its native tertiary structure is contained within the primary structure of the peptide chain itself. With this in mind, it was disappointing to the biochemists of the 1950s when the early protein structures did not reveal the governing principles in any particular detail. It soon became apparent that the proteins knew how they were supposed to fold into tertiary... 

In contrast, RNA occurs in multiple copies and various forms (Table 11.2). Cells contain up to eight times as much RNA as DNA. RNA has a number of important biological functions, and on this basis, RNA molecules are categorized into several major types messenger RNA, ribosomal RNA, and transfer RNA. Eukaryotic cells contain an additional type, small nuclear RNA (snRNA). With these basic definitions in mind, let s now briefly consider the chemical and structural nature of DNA and the various RNAs. Chapter 12 elaborates on methods to determine the primary structure of nucleic acids by sequencing methods and discusses the secondary and tertiary structures of DNA and RNA. Part rV, Information Transfer, includes a detailed treatment of the dynamic role of nucleic acids in the molecular biology of the cell. 

Thus, based on material applications, the following polymers are important natural rubber, coal, asphaltenes (bitumens), cellulose, chitin, starch, lignin, humus, shellac, amber, and certain proteins. Figure 4 shows the primary structures of some of the above polymers. For detailed information on their occurrence, conventional utilization, etc., refer to the references cited previously. 

If structural information of the protein target is available, e.g., a crystal structure, in silico screening of huge virtual compound libraries can be conducted by the use of docking simulations. Based on identified primary hits, structural variations of the ligand can be evaluated by computational modeling of the ligand-protein complex. 

Clusters Fa and Fb of photosystem I from cyanobacteria and chloro-plasts are distinguished by their EPR signatures (26, 27) and their reduction potentials (-520 mV for Fa and -580 mV for Fb Ref. (28). The assignment of cysteines in the primary sequence as ligands to individual clusters has been achieved by site-specific mutagenesis (29, Fig. 3), and structural information with regard to the environment of both clusters has been obtained by NMR (24). 

The preparation of polypeptide and polypeptide hybrid vesicles with predictable properties begins with proper synthesis of a primary structure. This section focuses on three different classes of procedures that are used to synthesize polypeptides. Although conjugation between the polypeptide and non-polypeptide blocks to form polypeptide hybrids is discussed briefly with the third class of synthesis procedures (Sect. 2.3), more detailed information regarding the synthesis and generation of polypeptide hybrid macromolecules are reviewed elsewhere [22-26]. 

In 1990, work was started to characterize the human genome which had been shown to consist of about 3 billion base pairs. The final result was announced in the year 2000. All of the chromosomes have been characterized. The human genome has been shown to contain some 30,000 genes (which are sections of the chromosome which code for specific proteins). Each cell produces the t T)e of proteins needed for it to function. The function of mRNA is to transfer information from the DNA. so as is to fix the limits of the protein needed. The vast majority of the proteins found in living organisms are composed of only 20 different kinds of amino acids, repeated many times and strung together in a particular order. Each type of protein has its own unique sequence of amino acids. This sequence, known as its primary structure, actually... 

The CrossFire Beilstein database is the world s largest compilation of chemical facts. This database indexes three primary data domains substances, reactions and literature. The substance domain stores structural information with aU associated facts and literature references, including chemical, physical and bioactivity data. The reaction domain details the preparation of substances, enabling scientists to investigate specific reaction pathways with reaction search queries. The literature domain includes citations, titles and abstracts, which are hyperhnked to the substance and reaction domain entries. It contains over 320 million experimental data, over 10 million reactions and data indexed from over 175 journals. 

DNA has two broad functions replication and expression. First, DNA must be able to replicate itself so that the information coded into its primary structure is transmitted faithfully to progeny cells. Second, this information must be expressed in some useful way. The method for this expression is through RNA intermediaries, which in turn act as templates for the synthesis of every protein in the body. The relationships of DNA to RNA and to protein are often expressed in a graphic syllogism called the central dogma. The concept was proposed by Crick in 1958 and was revised in 1970 to accommodate the discovery of the RNA-dependent DNA polymerase. Crick s original theory suggested that the flow of information was always from RNA to protein and could not be reversed, yet it allowed for the possibility of DNA synthesis from RNA. 

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