Structural highlights
4g27 is a 2 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , |
| Related: | 3sjq, 1g4y, 4g28 |
| Gene: | Kcnn2 (Buffalo rat), Calm1, Calm, Cam, Cam1, Calm2, Cam2, Camb, Calm3, Cam3, Camc (Buffalo rat) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[KCNN2_RAT] Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin.
Publication Abstract from PubMed
Small- and intermediate-conductance Ca(2+)-activated potassium channels, activated by Ca(2+)-bound calmodulin, have an important role in regulating membrane excitability. These channels are also linked to clinical abnormalities. A tremendous amount of effort has been devoted to developing small molecule compounds targeting these channels. However, these compounds often suffer from low potency and lack of selectivity, hindering their potential for clinical use. A key contributing factor is the lack of knowledge of the binding site(s) for these compounds. Here we demonstrate by X-ray crystallography that the binding pocket for the compounds of the 1-ethyl-2-benzimidazolinone (1-EBIO) class is located at the calmodulin-channel interface. We show that, based on structure data and molecular docking, mutations of the channel can effectively change the potency of these compounds. Our results provide insight into the molecular nature of the binding pocket and its contribution to the potency and selectivity of the compounds of the 1-EBIO class.
Identification of the functional binding pocket for compounds targeting small-conductance Ca(2+)-activated potassium channels.,Zhang M, Pascal JM, Schumann M, Armen RS, Zhang JF Nat Commun. 2012 Aug 28;3:1021. doi: 10.1038/ncomms2017. PMID:22929778[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhang M, Pascal JM, Schumann M, Armen RS, Zhang JF. Identification of the functional binding pocket for compounds targeting small-conductance Ca(2+)-activated potassium channels. Nat Commun. 2012 Aug 28;3:1021. doi: 10.1038/ncomms2017. PMID:22929778 doi:http://dx.doi.org/10.1038/ncomms2017
