Active site of proteins

There are very sophisticated programs to search these databases. The databases are used by chemists to design new chemical compounds and by dmg companies to design new dmgs for a great variety of diseases. Of special interest is the design of dmgs that fit into the active sites of proteins. 

Rarey, M., Weeing, S., and Lengauer, T. Placement of medium-sized molecular fragments into active sites of proteins. 

Why are the active sites of proteins found either as a cleft in the macromolecule or shallow depression on its surface and not thrust out where there is little hindrance for entry of the molecules Select a particular disease or illness and using the web find out what is known about its molecular biology including gene location. 

Since the mechanism underlying DSP is quite different, assays based on competition for the active site of protein phosphatase have been developed.41 42... 

In nature, many enzymes that hydrolyze phosphate monoesters are activated by two or more metal ions. They include alkaline phosphatase [79], purple acid phosphatase [80], inositol monophosphatase [81], and D-fructose 1,6-biphosphate 1-phosphatase [82]. The active sites of protein serine and threonine phosphatases also consist of dinuclear... 

What compounds of molecular weight below 250 Da will fit into the active site of protein Y and will bind strongly to it ... 

Placement of Medium-Sized Molecular Fragments Into Active Sites of Proteins. 

In general, iron snlfur clnsters are coordinated to native proteins via cysteine thiolate bonding, often in a Cys-X-Y-Cys motif (X, Y = nonsnlfhr containing amino acids). In clnsters with more than one iron atom, /u.2- or /rs-snlfur linkages connect the iron atoms within the clnster. At the active site of proteins, iron-snlfur clusters perform a variety of functions, including electron transport and enzymatic activity. 

Zahn, T.J., et al. (2000). Evalnation of isoprenoid conformation in solntion and in the active site of protein-farnesyl transferase nsing carbon-13 labehng in conjnnction with solntion and sohd state NMR. J Am Chem Soc 122 7153-7164. 

The percolation model suggests that it may not be necessary to have a rigid geometry and definite pathway for conduction, as implied by the proton-wire model of membrane transport (Nagle and Mille, 1981). For proton pumps the fluctuating random percolation networks would serve for diffusion of the ion across the water-poor protein surface, to where the active site would apply a vectorial kick. In this view the special nonrandom structure of the active site would be limited in size to a dimension commensurate with that found for active sites of proteins such as enzymes. Control is possible conduction could be switched on or off by the addition or subtraction of a few elements, shifting the fractional occupancy up or down across the percolation threshold. Statistical assemblies of conducting elements need only partially fill a surface or volume to obtain conduction. For a surface the percolation threshold is at half-saturation of the sites. For a three-dimensional pore only one-sixth of the sites need be filled. 

The direct electron transfer between the redox-active sites of proteins and electrodes is normally prohibited as a consequence of steric insulation by the protein matrix. Early studies demonstrated, however, that certain enzymes or redox proteins can exhibit electrical communication with electrode supports, and that electrically stimulated biocatalytic transformations can be driven by that process (Figure lA)... 

R347 N. S. Green, M. M. Miller and K. N. Houk, Evaluation of Isoprenoid Conformation in Solution and in the Active Site of Protein-Famesyl... 

Our results demonstrate that it is possible to trigger reactions in the buried active sites of proteins on micro- to nanosecond timescales. In particular, the direct photoreduction observed with tmRu-Fsbp-Im occurs on timescales that cannot be accessed using stopped-flow techniques. The preassociation of the Ru-wire and the enzyme also circumvents the time limits otherwise imposed by diffusion. 

As previously mentioned, these reactions are predictable extensions of reactions with monosaccharides. But perhaps the chemistry of oligosaccharides could be a more specific field. How is the reactivity of each hydroxyl group modified by the remainder of the complex sequence, by its configuration, and its conformation Are there functional groups which have lost all reactivity or else, on the contrary, unexpected preferred sites such as the active sites of proteins This area has not yet been explored with really complicated oligosaccharides. 

In addition to conventional sequence motifs (Prosite, BLOCKS, PRINTS, etc.), the compilation of structural motifs indicative of specific functions from known structures has been proposed [268]. This should improve even the results obtained with multiple (one-dimensional sequence) patterns exploited in the BLOCKS and PRINTS databases. Recently, the use of models to define approximate structural motifs (sometimes called fuzzy functional forms, FFFs [269]) has been put forward to construct a library of such motifs enhancing the range of applicability of motif searches at the price of reduced sensitivity and specificity. Such approaches are supported by the fact that, often, active sites of proteins necessary for specific functions are much more conserved than the overall protein structure (e.g. bacterial and eukaryotic serine proteases), such that an inexact model could have a partly accurately conserved part responsible for function. As the structural genomics projects produce a more and more comprehensive picture of the structure space with representatives for all major protein folds and with the improved homology search methods linking the related sequences and structures to such representatives, comprehensive libraries of highly discriminative structural motifs are envisionable. 

Most of the secondary amide cis peptide bonds found in protein structures occur in functionally important regions (e.g. dose to the active site of proteins). In the proximity of secondary amide cis peptide bonds the two neighboring Ca (i and i-1) atoms approach one another, enabling 7r-electron systems of aromatic side-chains to interact with the respective C,y atom. In this case the hydrogen atom of... 

Modeling of drug molecules binding to active sites of protein/receptor using... 

In biological systems, copper occurs as part of the active site of proteins or enzymes. The various ways in which copper is bound to these copper-binding centers are of special interest. 

The active site of protein kinase A is located in the 240-residue kinase core of the catalytic subunit. The kinase core, which is largely conserved in all protein kinases, is responsible for the binding of substrates (ATP and a target peptide sequence) and the subsequent transfer of a phosphate group from ATP to a serine, threonine, or tyrosine residue in the target sequence. The kinase core consists of a large domain and small one, with an intervening deep cleft the active site comprises residues located in both domains. 

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