Bacterial KcsA channel, crystal structure

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... 

At present, there is no crystal structure of the hERG channel. However, homology models have been built using crystal structures of bacterial potassium channels (e.g., MthK, KcsA [90, 91[). Blockers must cross the cell membrane and enter the channel... 

A number of different X-ray structures of bacterial potassium channels reveal the detailed atomic picture of the pore-forming part, helices S5 and S6 [9]. KcsA, which is crystallized in the closed conformation, has an overall structure similar to an inverted teepee [9a], Four identical subunits surround the ion-conducting pathway (Figure 8.2). Each subunit contains two full transmembrane helices, S5 and S6, as well as the P loop. The S6 helices line the central cavity, whereas the S5 helices are involved in interactions with the lipid environment. In the closed channel conformation the transmembrane helices meet at the cytosolic side to block the ion conduction path. In the open conformation of the channel, the S6 helix kinks at a conserved glycine residue to open the ion conduction path, as shown in the structure of the bacterial channel MthK [10], The ion conduction path is formed by the selectivity filter and the large water-filled central cavity. 

A recent structure-based lead-finding strategy was used for Kvl.5 inhibitors. The pore-forming domain of Kvl. 5 exhibits 54% sequence homology with the bacterial K+ channel KcsA from Streptomyces lividans, for which a crystal structure of the... 

Homology models for the sodium channel pore have been created using the crystal structure of the KcsA bacterial potassium selective channel. This model... 

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