Targeting the Small- and Intermediate-Conductance Ca2+-Activated Potassium Channels: The Drug-Binding Pocket at the Channel/Calmodulin Interface
文献类型：期刊论文
| 作者 | Cui, Meng2; Qin, Guangrong8; Yu, Kunqian8 ; Bowers, M. Scott3,4,5,6,7; Zhang, Miao1,2
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| 刊名 | NEUROSIGNALS
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| 出版日期 | 2014 |
| 卷号 | 22期号:2页码:65-78 |
| 关键词 | Small- and intermediate-conductance Ca2+-activated potassium channels Small-molecule positive modulators Structure-based drug discovery Ataxia Alcohol use disorders Parkinson's disease |
| ISSN号 | 1424-862X |
| DOI | 10.1159/000367896 |
| 文献子类 | Review |
| 英文摘要 | The small- and intermediate-conductance Ca2+-activated potassium (SK/IK) channels play important roles in the regulation of excitable cells in both the central nervous and cardiovascular systems. Evidence from animal models has implicated SK/IK channels in neurological conditions such as ataxia and alcohol use disorders. Further, genome-wide association studies have suggested that cardiovascular abnormalities such as arrhythmias and hypertension are associated with single nucleotide polymorphisms that occur within the genes encoding the SK/IK channels. The Ca2+ sensitivity of the SK/IK channels stems from a constitutively bound Ca2+-binding protein: calmodulin. Small-molecule positive modulators of SK/IK channels have been developed over the past decade, and recent structural studies have revealed that the binding pocket of these positive modulators is located at the interface between the channel and calmodulin. SK/IK channel positive modulators can potentiate channel activity by enhancing the coupling between Ca2+ sensing via calmodulin and mechanical opening of the channel. Here, we review binding pocket studies that have provided structural insight into the mechanism of action for SK/IK channel positive modulators. These studies lay the foundation for structure-based drug discovery efforts that can identify novel SK/IK channel positive modulators. (C) 2014 S. Karger AG, Basel |
| WOS关键词 | INTRINSICALLY DISORDERED PROTEIN ; CA2+-DEPENDENT K+-CHANNEL ; MIDDLE CEREBRAL-ARTERY ; SPINOCEREBELLAR ATAXIA ; CEREBELLAR-ATAXIA ; SK CHANNELS ; DOPAMINERGIC-NEURONS ; MESENTERIC-ARTERIES ; ATRIAL-FIBRILLATION ; FUNCTIONAL ROLES |
| 资助项目 | American Heart Association[13SDG16150007] ; National Institutes of Health[S10RR027411] ; National Institutes of Health[P50AA022537] ; Alcohol Beverage Medical Research Foundation[00000000] ; National High Technology Research and Development Program of China[2012AA020301] ; National High Technology Research and Development Program of China[2012AA01A305] ; Chinese Academy of Sciences Project[KSZD-EW-L09-4] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics ; Cell Biology ; Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000353336700001 |
| 出版者 | KARGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277243]  |
| 专题 | 药物发现与设计中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Zhang, Miao |
| 作者单位 | 1.Chapman Univ, Sch Pharm, Dept Biomed & Pharmaceut Sci, Irvine, CA USA; 2.Virginia Commonwealth Univ, Sch Med, Dept Physiol & Biophys, Richmond, VA 23298 USA; 3.Virginia Commonwealth Univ, Sch Med, Dept Psychiat, Richmond, VA 23298 USA; 4.Virginia Commonwealth Univ, Sch Med, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA; 5.Virginia Commonwealth Univ, Sch Med, Dept Neurosci, Richmond, VA 23298 USA; 6.Virginia Commonwealth Univ, Sch Med, Inst Drug & Alcohol Studies, Richmond, VA 23298 USA; 7.Virginia Commonwealth Univ, Sch Med, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA; 8.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cui, Meng,Qin, Guangrong,Yu, Kunqian,et al. Targeting the Small- and Intermediate-Conductance Ca2+-Activated Potassium Channels: The Drug-Binding Pocket at the Channel/Calmodulin Interface[J]. NEUROSIGNALS,2014,22(2):65-78. |
| APA | Cui, Meng,Qin, Guangrong,Yu, Kunqian,Bowers, M. Scott,&Zhang, Miao.(2014).Targeting the Small- and Intermediate-Conductance Ca2+-Activated Potassium Channels: The Drug-Binding Pocket at the Channel/Calmodulin Interface.NEUROSIGNALS,22(2),65-78. |
| MLA | Cui, Meng,et al."Targeting the Small- and Intermediate-Conductance Ca2+-Activated Potassium Channels: The Drug-Binding Pocket at the Channel/Calmodulin Interface".NEUROSIGNALS 22.2(2014):65-78. |
入库方式： OAI收割
来源：上海药物研究所
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