Primary sequence

Most reactions in cells are carried out by enzymes [1], In many instances the rates of enzyme-catalysed reactions are enhanced by a factor of a million. A significantly large fraction of all known enzymes are proteins which are made from twenty naturally occurring amino acids. The amino acids are linked by peptide bonds to fonn polypeptide chains. The primary sequence of a protein specifies the linear order in which the amino acids are linked. To carry out the catalytic activity the linear sequence has to fold to a well defined tliree-dimensional (3D) stmcture. In cells only a relatively small fraction of proteins require assistance from chaperones (helper proteins) [2]. Even in the complicated cellular environment most proteins fold spontaneously upon synthesis. The detennination of the 3D folded stmcture from the one-dimensional primary sequence is the most popular protein folding problem. 

RNA structures, compared to the helical motifs that dominate DNA, are quite diverse, assuming various loop conformations in addition to helical structures. This diversity allows RNA molecules to assume a wide variety of tertiary structures with many biological functions beyond the storage and propagation of the genetic code. Examples include transfer RNA, which is involved in the translation of mRNA into proteins, the RNA components of ribosomes, the translation machinery, and catalytic RNA molecules. In addition, it is now known that secondary and tertiary elements of mRNA can act to regulate the translation of its own primary sequence. Such diversity makes RNA a prime area for the study of structure-function relationships to which computational approaches can make a significant contribution. 

The events and causal factors chart for this incident is shown in Figure 7.9. The primary sequence of events is shown horizontally in bold boxes. Secondary events are shown in the other boxes, and conditions are in ovals. From the diagram three causal factors were identified and carried forward to the Root Cause Coding to establish the root causes of the causal factors. 

The four mammalian ARs are members of the rhodopsin-like Class A family of GPCRs, which contain seven transmembrane helical domains ( TMs). Character istics of the four subtypes of the human ARs, length of their primary sequences, their chromosomal localization, and their signaling pathways are given in Table 1. The A2a receptor is considerably longer than the other three subtypes, due to its extended carboxy-terminal. 

Adenosine Receptors. Figure 3 An alignment of the primary sequences of the four human AR subtypes. Regions of conservation are highlighted. indicates the most conserved (X.50) residue in each TM region. Bold residues correspond to those indicated in Table 1. The A2A receptor is truncated in the carboxy-terminal region. 

This branch of bioinformatics is concerned with computational approaches to predict and analyse the spatial structure of proteins and nucleic acids. Whereas in many cases the primary sequence uniquely specifies the 3D structure, the specific rules are not well understood, and the protein folding problem remains largely unsolved. Some aspects of protein structure can already be predicted from amino acid content. Secondary structure can be deduced from the primary sequence with statistics or neural networks. When using a multiple sequence alignment, secondary structure can be predicted with an accuracy above 70%. 

In cyclic nucleotide-regulated channels, this domain serves as a high-affinity binding site for 3-5 cyclic monophosphates. The CNBD of channels has a significant sequence similarity to the CNBD of most other classes of eukaryotic cyclic nucleotide receptors and to the CNBD of the prokaryotic catabolite activator protein (CAP). The primary sequence of CNBDs consists of approximately 120 amino acid residues forming three a-helices (oA-aC) and eight (3-strands ( 31- 38). 

The primary sequence of proteins, with identical function varies within different species by natural mutations of amino acids. With increasing distance in the evolutionary process the number of variations between the sequences of proteins increase. 

On the basis of primary sequence considerations, 7Fe Fds can be subdivided into at least two major classes. The first class (Azotobacter-type) is typified by the structurally characterized A. vinelandii Fdl (18, 69, 123, 124) and has two groups of coordinating cysteine residues with consensus sequences of -C-X2-X-K-X3-C-Xg-g-P-V- and -g-Xs-C-Xs-Q-Xg-C-P- for the first and second groupings, respectively. The C and C residues ligate the [FegS4] and [Fe4S4l clusters, respectively, and the X residue is C, V, T, or E see Table II. In addition to the anomalous arrangement of cysteine resi-... 

As noted in Section II,C parts of the primary sequences of Fe proteins have strong similarities to those of various GTPases and ATPases. With these enzymes, aluminum fluoride (AlFf) has been... 

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). 

Clusters Fa tmd Fb can be (photo-)reduced by light-induced charge separation within the RC complex at cryogenic temperatures. Since, under these conditions, only one electron is injected into the Fa/Fb-protein, and since furthermore the EPR spectra of Fa and Fb are significantly different, a straightforward assignment of individual clusters to the cluster-binding motifs in the primary sequence was... 

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