Binding site location

An interesting study on the rebinding of diketones to imprinted polymers was reported by Shea and Sasaki [69], Polymers were prepared by copolymerisation of the corresponding Z w-ketal as template with meta-di-isopropenylbenzene as cross-linking monomer (Fig. 2.15). The 6w-ketal is hydrolysed with acid freeing the 

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Fig. 10. Calculated sodium ion single channel currents for the malonyl Gramicidin channel and comparison with experimental data points using four different models all of which fit the data well but only one of which, B., is correct. The point to be made is that both the independent determination of rate constants and of the binding site locations are required.

The P-site of adenylyl cyclase inhibits cyclic AMP accumulation. Since P, and P2 receptors are located on the cell surface, they bind purines or pyrimidines in the extracellular space. There also is an adenosine binding site located intracellularly on the enzyme adenylyl cyclase (see Ch. 21). This is referred to as the P-site of adenylyl cyclase. Binding of adenosine and other purines, notably 3 AMP, 2 deoxy-3 -ATP and 2, 5 -dideoxyadenosine to this site, inhibits adenylyl cyclase activity [8]. The P-site of adenylyl cyclase and other intracellular purine binding sites are not classified as purinergic receptors. 

Bali M, Akabas MH. 2004. Defining the propofol binding site location on the GABAa receptor. Mol Pharmacol 65 68-76. 

The current model for Mg + transport is illustrated in Figure 8 and is believed to be controlled by a magnesium sensor consisting of two specific Mg + binding sites located on the outside of the funnel in the a a sandwich domain that spans the wiUow helices and /3-sheets ° . Studies of similar binding sites in other proteins indicates that these sites will probably have an affinity for Mg + that is slightly less than the average free concentration of Mg + in cells . When the concentration of Mg in the cell drops below... 

Linezolid inhibits protein synthesis by preventing formation of the ribosome complex that initiates protein synthesis. Its unique binding site, located on 23S ribosomal RNA of the 50S subunit, results in no cross-resistance with other drug classes. Resistance is caused by mutation of the linezolid binding site on 23S ribosomal RNA. 

Since the lumenal site of microtubules was well supported by the structural data and also by the fact that mutations in the lumenal site confer resistance to taxanes [45], an alternative mechanism with binding to an initial exposed binding site located in pore type I of the microtubule wall and later transportation of the ligand to the lumenal site was proposed in [22] (Fig. 9). 

From the kinetics of ligand binding to microtubules we can obtain valuable information about the way paclitaxel microtubule stabilizing agents reach their binding site. They bind to an external binding site located in the pores of the microtubule wall from which they are totally or partially relocated to an inner luminal site. 

The identification of the binding site location within tubulin, together with the clarification of the binding mode for some representative destabilizing compounds, opened new perspectives to modeling studies in this field, making the application possible not only of ligand-based, but also structure-based approaches. 

Medek A, Hajduk PJ, Mack J, Fesik SW, The use of differential chemical shifts for determining the binding site location and orientation of protein-bound ligands, J. Am. Chem. Soc., 122 1241-1242, 2000. 

Initial studies of the NMDA receptor, which focused on the PCP binding site located inside the ion channel, found no marked changes in the hippocampus in schizophrenia (Kornhuber et al., 1989 ... 

Whether neurotensin acts directly at NTRi receptors on TIDA neurons is not clear. The presence of dense neurotensin binding sites located within the mediobasal hypothalamus (Goedert et al., 1985 Meister et al., 1989) and the observation that single unit activity of approximately 70% of all DM-ARC neurons is stimulated by neurotensin in vitro suggest a localized action on (or near) TIDA neurons (Lin and Pan, 1993). Moreover, the presence of synaptic connections between neurotensin-IR and TH-IR neurons in the DM-ARC is consistent with a direct action of neurotensin on TIDA neurons (Marcos et al., 1996a). On the other hand, TIDA neurons do not normally express appreciable amounts of neurotensin receptor mRNA like mesotelencephalic DA neurons... 

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