Proteins functions

From the biomedical perspective, structural and kinetic studies are incomplete without determining the function of the protein. In the discussion of posttransla-tional modifications and noncovalent complexes, we have already indicated their important role in regulating the role a protein plays. In addition to biological function, protein-based drug and vaccine design also requires the elucidation of their mechanism of action. From heart disease to cancer, there are many examples in this volume showing the variety of implicated proteins [36]. Conversely, structural discrepancies in proteins are shown to result in disease states. 

Even if the participating protein segments are discontinuous, epitopes can also be identified by hydrogen-deuterium exchange. The components of the noncovalent complex are deuterated in D2O environment and allowed to react. When the 

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Proteins are biopolymers formed by one or more continuous chains of covalently linked amino acids. Hydrogen bonds between non-adjacent amino acids stabilize the so-called elements of secondary structure, a-helices and / —sheets. A number of secondary structure elements then assemble to form a compact unit with a specific fold, a so-called domain. Experience has shown that a number of folds seem to be preferred, maybe because they are especially suited to perform biological protein function. A complete protein may consist of one or more domains. 

The SWISS-PROT database [36] release 40.44 (February, 2003) contains over 120 000 sequences of proteins with more than 44 million amino adds abstracted from about 100 000 references. Besides sequence data, bibHographical references, and taxonomy data, there are highly valuable annotations of information (e.g., protein function), a minimal level of redundancy, and a high level of integration with other databases (EMBL, PDB, PIR, etc.). The database was initiated in 1987 by a partnership between the Department of Medicinal Biochemistry of the University of Geneva, Switzerland, and the EMBL. Now SWISS-PROT is driven as a joint project of the EMBL and the Swiss Institute of Bioinformatics (SIB). 

Foldmg/unfoldmg Protein functionality (10 -10 s) more than 10 A... 

Morr, C.V., "Current Status of Soy Protein Functionality in Food Systems," Journal of the American Oil Chemists Society 67 (5) 265-27 (1990). 

FIGURE 5.13 Two basic types of biological transport are (a) transport within or between different cells or tissues and (b) transport into or out of cells. Proteins function in both of these phenomena. For example, the protein hemoglobin transports oxygen from the lungs to actively respiring tissues. Transport proteins of the other type are localized in cellular membranes, where they function in the uptake of specific nutrients, such as glucose (shown here) and amino acids, or the export of metabolites and waste products. 

Creighton, T. E., ed., 1997. Protein Function—A Practical Approach, 2nd ed. Oxford IRL Pre.s.s at Oxford University Press. 

Nearly all biological processes involve the specialized functions of one or more protein molecules. Proteins function to produce other proteins, control all aspects of cellular metabolism, regulate the movement of various molecular and ionic species across membranes, convert and store cellular energy, and carry out many other activities. Essentially all of the information required to initiate, conduct, and regulate each of these functions must be contained in... 

Chemistry of photoproteins (modified proteins with luminescent covalent-linked heterocyclic fragments) as interface between bioactive molecules and protein function 98PAC2085. 

Acyl azide, amines from, 935 Acyl carrier protein, function of, 1 140 Acyl cation, electrostatic potential map of, 558... 

Also databases of scientific literature (such as PUBMED, MEDLINE) provide additional functionality, e.g. they can search for similar articles based on word-usage analysis. Text recognition systems are being developed that automatically extract knowledge about protein function from the abstracts of scientific articles, notably on protein-protein interactions. 

More detailed aspects of protein function can be obtained also by force-field based approaches. Whereas protein function requires protein dynamics, no experimental technique can observe it directly on an atomic scale, and motions have to be simulated by molecular dynamics (MD) simulations. Also free energy differences (e.g. between binding energies of different protein ligands) can be characterised by MD simulations. Molecular mechanics or molecular dynamics based approaches are also necessary for homology modelling and for structure refinement in X-ray crystallography and NMR structure determination. 

Chloride channels are membrane proteins that allow for the passive flow of anions across biological membranes. As chloride is the most abundant anion under physiological conditions, these channels are often called chloride channels instead of anion channels, even though other anions (such as iodide or nitrate) may permeate better. As some CLC proteins function as CF-channels, whereas other perform CF/H+-exchangers are also mentioned here. 

Phosphorylation is the reversible process of introducing a phosphate group onto a protein. Phosphorylation occurs on the hydroxyamino acids serine and threonine or on tyrosine residues targeted by Ser/Thr kinases and tyrosine kinases respectively. Dephosphorylation is catalyzed by phosphatases. Phosphorylation is a key mechanism for rapid posttranslational modulation of protein function. It is widely exploited in cellular processes to control various aspects of cell signaling, cell proliferation, cell differentiation, cell survival, cell metabolism, cell motility, and gene transcription. 

Very large Serine/Threonine kinases and the molecular Target of Rapamycin, a naturally occurring secondary metabolite, TOR proteins function within multiprotein complexes to couple cell growth and stress responses to environmental and developmental cues. 

Biochemical purification of TOR demonstrated that this protein functions as the catalytic component of two distinct multiprotein complexes known as TOR complex 1 (TORC1) and TOR complex 2 (TORC2). Like TOR, these complexes appear to have been structurally and functionally conserved form yeast to man. The mammalian equivalents are known as mTORCl and mTORC2. 

Ubiquitin/Proteasome. Figure 2 Functional consequences of ubiquitin linkage. Substrates (blue bars) are linked via lysine residues (K) to ubiquitin or ubiquitin chains, (a) Attachment of chains connected via Lysines in position 48 of ubiquitin (K48) targets substrates for proteasomal degradation. In contrast modification of one (b) or multiple (c) lysines by a single ubiquitin molecule mediates novel protein interactions or initiates endocytosis. Conjugation of K63-linked polyubiquitin (d) alters protein function and can also serve as a signal for endocytosis. 

The macrolides are bacteriostatic or bactericidal in susceptible bacteria The drugs act by binding to cell membranes and causing changes in protein function. 

There are four levels of sUucture observed in proteins [9] and it is important that once the molecular weight of a protein has been determined that these are also elucidated in order that the way in which the protein functions may be understood. 

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