Protein binding site

The GRID program [Goodford 1985] that is used for finding energetically favourable regions in protein binding sites uses a direction-dependent 6-4 fxmction ... 

IV, ] Ruppert and A N Jain 1996. Hammerhead Fast, Fully Automated Docking of Flexible ands to Protein Binding Sites. Chemistry and Biology 3 449-462. 

The absorption of sulfonylureas from the upper gastrointestinal tract is faidy rapid and complete. The agents are transported in the blood as protein-bound complexes. As they are released from protein-binding sites, the free (unbound) form becomes available for diffusion into tissues and to sites of action. Specific receptors are present on pancreatic islet P-ceU surfaces which bind sulfonylureas with high affinity. Binding of sulfonylureas to these receptors appears to be coupled to an ATP-sensitive channel to stimulate insulin secretion. These agents may also potentiate insulin-stimulated glucose transport in adipose tissue and skeletal muscle. 

Sulfaphenazole (684) and sulfazamet (685) are both examples of relatively short acting sulfonamides (B-80MI40406) and their antibacterial activity has been tested against Escherichia coli, the former being more effective than the latter. Sulfaphenazole also displaces sulfonyl ureas from protein binding sites on human serum albumin and consequently increases the concentration of the free (active) drug and produces a more intense reaction that may result in hypoglycemia. 

Figure 8.1 A region of DNA in the related bacteriophages lambda, 434, and P22 that controls the switch for synthesis of new phage particles. Two structural genes are involved in this switch one coding for a repressor protein and one coding for the Cro protein. Between these genes there is an operator region (OR) that contains three protein binding sites—ORl, OR2, and OR3.

Drug Interactions During Distribution Displacement from Plasma Protein Binding Sites... 

Wu, B., Williams, G.T., Morimoto, R.I. (1987). Deletion of three protein binding sites in the serum-regulated promoter of the human gene encoding the 70 kDa heat shock protein. Proc Natl. Acad. Sci. USA 84, 2203-2207. 

The administration of cloflbrate to a patient taking warfarin will potentiate the anticoagulant effect of warfarin by displacing It from Its protein binding site (7). This Interaction will cause... 

The method utilizing ID NMR is simple and eonvenient. Henee the NMR method diseussed here ean be applied to the systematie investigation of the membrane irug inter-aetions, elosely related to the vital function in biomembranes. It is expected that the application can be extended to the lipid-peptide interaction and protein uptake. We are now applying the method to apolipoprotein binding with lipid bilayers and emulsions. Preferential protein binding sites in membranes can be specified by NMR on the molecular level. 

In this section, a number of case studies (Table 5) in which different types of VS methods are combined into a hybrid workflow. Often these combine a fast, ligand or pharmacophore-based method with a later docking method. The latter is useful at the inspection stage as it allows the molecule to be reviewed within the context of the protein binding site. A poor binding pose can be an indicator of a poor fit. Furthermore, possible interactions outside the scope of the molecules used to train the ligand-based method can be identified. 

Damaj BB, McColl SR, Neote K, et al. Identification of G-protein binding sites of the human interleukin-8 receptors by functional mapping of the intracellular loops. FASEB J 1996 10(12) 1426-1434. 

Sytnik A, Kasha M (1994) Excited-state intramolecular proton transfer as a fluorescence probe for protein binding-site static polarity. Proc Natl Acad Sci USA 91 8627-8630... 

Consider what happens when a nonoptimal ligand binds to the protein. The binding of this modified ligand is much weaker not because it s not the right size to fit into the protein-binding site, but because the complementary group on the protein loses a favorable interaction with water that is not replaced by an equally favorable interaction with the ligand (Fig. 2-6). 

A (590). Ruthenium Red (Section III.D.3) affects the performance of calcium channels (529,591) by interaction with carboxylates at protein-binding sites. The Ruthenium Red is said to block the channel by forming a 1 1 complex at a site in the extracellular entrance to the channel pore, at least for certain neuronal voltage-gated calcium channels (592). 

D. S. Dwyer and R. J. Bradley, Chemical properties of alcohols and their protein binding sites. Cell. Mol. Life Sci. 57, 265 275 (2000). 

Proteins binding sites denaturation site accessibility dynamics distances conformational transition... 

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