Ion channels structure

Pedersen, S. E., Lurtz, M. M., Papineni, R. V. L Ligand-binding methods for analysis of ion channel structure and fimction. Methods Enzymol. 1999, 294, 117-135. 

Therefore, the authors have synthesized heptakis(carboxymethyl)-substituted a-cyclodextrin which was combined with hydrophobic ammonium to afford 9 (Figure 13), whereby the number of carboxylate-ammonium ion pairs was regulated to six. This compound was incorporated into BUM and subjected to singlechannel current measurements. The current-voltage plot gave a single straight line to afford a conductance level of 7.7 pS under several different experimental conditions. Then the modified cyclodextrin successfully controlled the ion channel structure and therefore the conductance. 

Figure 26. Scheme for the control of ionic fluxes by light irradiation. trans-Azo ammonium, covering the hydrophilic oligoether parts from the outside, can stabilize the supramolecular ion channel structure, while cis cannot because of its bent structure. Therefore, trans-azo generates ion channel currents, while for c/sonly small leak currents across the membrane. 

Left and center Two gramicidin A molecules associate to span a cell membrane. Right Axial view showing ion channel. [Structure from B. Roux, "Computational Studies of the Gramicidin Channel." Acc. Chem. Res. 2002,35,366. based on solid-state nuclear magnetic resonance. Schematic at left from L. Stryer. Biochemistry,... 

Fig. 23. Schematic representation of different possible types of ion channel structures (from left to right) stack, string, rack, pipe of macrocycles, helical strand, two half-channel units, self-aggregated and macrocycle core bearing bundles of chains.

Structure-based lead finding requires a target 3D structure to start with. However, experimental elucidation of ion channel structures either NMR or X-ray crystallography is extremely difficult to achieve. Nevertheless, homology modeling of closely homologous channels to KcsA or MthK, for which 3D structures are available (see Section 8.2), makes this approach feasible. 

Jin, R., Homing, M., Mayer, M. L., and Gouaux, E. (2002). Mechanism of activation and selectivity in a ligand-gated ion channel Structural and functional studies of GluR2 and quisqualate. Biochemistry 41, 15635-15643. 

A. Abbott, Ion Channel Structures They Said it Couldn t be Done, Nature, 418, 268-269 (2002). 

The Structure of a Potassium Ion Channel Is an Archetype for Many Ion-Channel Structures... 

Figure 2. A schematic representation of ion channel structure depicting the principal components that determine channel function.

Ion Channel Structure and Function Basic Principles and Mechanisms 391... 

ION CHANNEL STRUCTURE AND FUNCTION BASIC PRINCIPLES AND MECHANISMS... 

In addition to these ion channel structural considerations, it should be noted that channels can be expressed in different isoforms encoded by distinct genes or as different splice variants that may be selectively expressed in certain cell types or during certain developmental stages of an organism. These structural variations dramatically increase the level of channel functional diversity. 

In order to develop new ion channel targeted drugs, we must clearly understand ion channel struc-ture-to-function relationships. We now know the crystal protein structure of the bacterial KcsA channel, but soon we will have additional crystal ion-channel structures. In the past several decades, ion channel research has been one of the most rapidly developing... 

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